Introduction The reliance on the United States Medical Licensing Examination (USMLE) Step 1 scores in residency selection creates problems for osteopathic medical students and the programs that review their applications. Although many osteopathic students take the USMLE to improve their standing for residency selection, students who score poorly may harm their candidacy. Simultaneously, programs unfamiliar with the Comprehensive Osteopathic Medical Licensing Examination (COMLEX-USA) may struggle to evaluate applicants who have not taken USMLE. Objective To determine the association between COMLEX-USA Level 1 and USMLE Step 1 scores and derive an equation that could be used to predict USMLE performance or approximate USMLE scores for applicants who have only taken COMLEX-USA. Methods We reviewed COMLEX-USA Level 1 and USMLE Step 1 scores for all students at the Lake Erie College of Osteopathic Medicine (LECOM), Bradenton campus, from January 2012 until December 2016. Linear regression was used to evaluate the relationship between COMLEX-USA Level 1 and USMLE Step 1 scores. Results Overall, 2097 students took both examinations during the study period. Every one-point increase in COMLEX-USA was associated with a 0.15 point increase in USMLE Step 1 score (standard error 11.5; model R 0.56). On average, students scored 30 percentile points lower on USMLE Step 1 than on COMLEX-USA, and 24% of students scoring <500 on COMLEX-USA Level 1 failed USMLE Step 1. Conclusions Students or programs interested in predicting performance on USMLE Step 1 from performance on COMLEX-USA Level 1 can do so with the following equation: USMLE Step 1 = 0.15 (COMLEX-USA Level 1) + 138.7.