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| Career ERA Leaderboard | |
| * - Indicates Hall of Fame Bold - Indicates active player |
| Rank | Player | ERA | IP | Years | Single Season Leaderboard |
| 1. | James Yim * | 2.126 | 4445.9 | 2003-2021 | |
| 2. | Kevin Smith | 2.227 | 2599.0 | 2019-2029 | |
| 3. | Edgardo Castillo * | 2.270 | 3758.6 | 2001-2018 | |
| 4. | Hugo Holt * | 2.322 | 1108.3 | 2006-2021 | |
| 5. | Deangelo Ramos * | 2.415 | 1166.3 | 2003-2020 | |
| 6. | Clarence McNatt * | 2.416 | 2894.0 | 2003-2017 | |
| 7. | Alfonso Font | 2.428 | 1275.3 | 2015-2029 | |
| 8. | Art Toczek * | 2.430 | 2240.3 | 2011-2023 | |
| 9. | Ben Lamela | 2.434 | 3342.6 | 2008-2025 | |
| 10. | Leo Cleland * | 2.445 | 2815.6 | 2004-2017 | |
| 11. | Chad Schmidt | 2.485 | 3346.6 | 2015-2029 | |
| 12. | Allen Sampley | 2.495 | 1702.3 | 2007-2021 | |
| 13. | Aaron Bacon * | 2.510 | 3356.0 | 2000-2012 | |
| 14. | Richard San Juan | 2.543 | 3143.3 | 2017-2029 | |
| 15. | Donald Granger * | 2.555 | 1025.0 | 2003-2017 | |
| 16. | Ryan Turner * | 2.579 | 3744.9 | 2001-2021 | |
| 17. | Lowell Stang * | 2.596 | 2987.9 | 2007-2021 | |
| 18. | Robert Garza * | 2.632 | 2458.6 | 2004-2015 | |
| 19. | Russell Henikar | 2.679 | 1004.3 | 2009-2024 | |
| 20. | Joseph Seybert | 2.686 | 1290.0 | 2000-2005 | |
| 21. | Todd Neary | 2.708 | 2286.6 | 2019-2029 | |
| 22. | Kenneth Krahn | 2.708 | 1711.6 | 2005-2013 | |
| 23. | J.L. Carrillo | 2.734 | 1629.3 | 2018-2026 | |
| 24. | Darryl Leekong | 2.737 | 1186.9 | 2011-2026 | |
| 25. | Larry Burkholder | 2.769 | 1105.0 | 2011-2024 | |
| 26. | Ralph Ives | 2.779 | 2623.6 | 2018-2029 | |
| 27. | David Echegaray | 2.790 | 4812.6 | 2003-2026 | |
| 28. | Scott Bartell | 2.829 | 4101.3 | 2003-2021 | |
| 29. | Luis Alou | 2.858 | 1429.6 | 2014-2028 | |
| 30. | Amadeo Villerreal | 2.870 | 1712.0 | 2018-2026 | |
| 31. | Wilfredo Arroyo | 2.876 | 1658.6 | 2023-2029 | |
| 32. | Dennis Wright * | 2.878 | 3380.6 | 2001-2014 | |
| 33. | Billy-Bob Suggs | 2.890 | 1588.3 | 2003-2021 | |
| 34. | David Evans | 2.900 | 1412.3 | 2000-2006 | |
| 35. | Cougar Koon | 2.913 | 1093.6 | 2020-2029 | |
| 36. | Shiro Ogusuku | 2.936 | 1014.7 | 2025-2029 | |
| 37. | Osvaldo Pedraza | 2.941 | 3311.0 | 2003-2017 | |
| 38. | Tyler Lattimore | 2.943 | 1073.3 | 2014-2029 | |
| 39. | Mark Trowers | 2.945 | 3535.9 | 2010-2025 | |
| 40. | Armando Mesta | 2.963 | 1366.7 | 2023-2029 | |
| 41. | Roderigo Pequero | 2.971 | 2668.6 | 2018-2029 | |
| 42. | Rusty Skittles | 2.976 | 2706.3 | 2007-2020 | |
| 43. | Henrique Reynoso | 2.998 | 1564.3 | 2011-2027 | |
| 44. | Vern Taylor | 3.000 | 1191.0 | 2008-2022 | |
| 45. | Leonard Lubbers | 3.006 | 2356.6 | 2003-2013 | |
| 46. | Xalbador Laguna | 3.007 | 2146.0 | 2019-2029 | |
| 47. | Geoff Stagner | 3.008 | 2609.0 | 2011-2025 | |
| 48. | Blaine Titsworth | 3.025 | 1930.6 | 2000-2009 | |
| 49. | Manuel Nieves | 3.026 | 2186.3 | 2020-2029 | |
| 50. | George Aybar | 3.037 | 2359.3 | 2007-2019 | |
| 51. | Thomas Showers * | 3.043 | 3348.0 | 2000-2013 | |
| 52. | Jack Fasano | 3.066 | 1053.7 | 2000-2005 | |
| 53. | John Demar | 3.074 | 1057.0 | 2000-2006 | |
| 54. | Jonathan Alexander | 3.078 | 2154.6 | 2019-2029 | |
| 55. | Armando Quinonez * | 3.087 | 1638.6 | 2000-2007 | |
| 56. | Jose Castillo | 3.092 | 1010.0 | 2008-2014 | |
| 57. | William Roberts | 3.098 | 2103.6 | 2008-2021 | |
| 58. | Mark Torrence | 3.101 | 2896.3 | 2002-2015 | |
| 59. | Tobias Escobar | 3.108 | 2817.9 | 2006-2019 | |
| 60. | Pete Leighburn | 3.123 | 1550.7 | 2023-2029 | |
| 61. | Adam Burton | 3.130 | 2164.9 | 2009-2022 | |
| 62. | Willie Wilson | 3.142 | 1936.6 | 2017-2029 | |
| 63. | J.J. Cobb | 3.145 | 3210.6 | 2000-2014 | |
| 64. | Harry Swint | 3.150 | 1377.0 | 2000-2005 | |
| 65. | Donte Dasilva | 3.161 | 3018.0 | 2003-2017 | |
| 66. | Melvin Bohrer | 3.168 | 1971.3 | 2011-2024 | |
| 67. | Wayne Rossignol | 3.178 | 1569.0 | 2016-2029 | |
| 68. | Wayne Sorely | 3.184 | 1648.0 | 2021-2029 | |
| 69. | Dan Coningsby | 3.190 | 1388.0 | 2023-2029 | |
| 70. | David Bonneau | 3.191 | 1427.3 | 2021-2029 | |
| 71. | Rafael Souza | 3.191 | 2287.6 | 2003-2022 | |
| 72. | Pedro Ceasar | 3.195 | 1160.6 | 2000-2009 | |
| 73. | Samson Steele * | 3.200 | 2596.0 | 2000-2011 | |
| 74. | Danny Day | 3.201 | 2527.6 | 2014-2026 | |
| 75. | Ty Mercury | 3.206 | 1499.0 | 2008-2016 | |
| 76. | Jack Pinkston | 3.207 | 1175.9 | 2016-2029 | |
| 77. | Kelvin Palen | 3.210 | 2641.3 | 2000-2010 | |
| 78. | Dennis Morelock * | 3.216 | 4013.6 | 2003-2017 | |
| 79. | Claudio Romeo | 3.216 | 1774.3 | 2000-2008 | |
| 80. | Jacob Perl | 3.221 | 2679.6 | 2016-2029 | |
| 81. | Francisco Apodaca | 3.227 | 1344.3 | 2002-2017 | |
| 82. | Robert Mansell | 3.235 | 1435.6 | 2012-2025 | |
| 83. | Andrew Albury | 3.245 | 2407.3 | 2001-2014 | |
| 84. | Ramon Cordova | 3.249 | 2756.6 | 2017-2029 | |
| 85. | Hugh Hoots | 3.257 | 3766.6 | 2002-2018 | |
| 86. | Curtis Yoo | 3.257 | 2331.9 | 2013-2027 | |
| 87. | David Scoggin | 3.269 | 1654.6 | 2000-2011 | |
| 88. | Robert Harris | 3.271 | 1973.0 | 2011-2023 | |
| 89. | Dmitrij Mitskevich | 3.276 | 1244.3 | 2002-2006 | |
| 90. | Bill Rowley | 3.279 | 1572.6 | 2010-2020 | |
| 91. | James Alexander | 3.293 | 2806.6 | 2011-2026 | |
| 92. | Stuart Whyte | 3.296 | 2143.3 | 2011-2022 | |
| 93. | Steven Williams * | 3.307 | 3524.0 | 2002-2017 | |
| 94. | Benicio Andaverde | 3.311 | 2653.3 | 2016-2029 | |
| 95. | William Piccolo | 3.312 | 1146.6 | 2000-2006 | |
| 96. | Robby Butler | 3.320 | 1374.3 | 2000-2007 | |
| 97. | Edward Goffe | 3.328 | 1555.0 | 2009-2018 | |
| 98. | Benny Suarez | 3.335 | 2730.9 | 2016-2029 | |
| 99. | Humberto Deleon | 3.339 | 3174.9 | 2014-2029 | |
| 100. | Charlie Clowers | 3.341 | 2168.3 | 2008-2019 |
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