The aims of the study are to identify factors contributing to preliminary interpretive discrepancies on overnight radiology resident shifts and apply this data in the context of known literature to draw parallels to attending overnight shift work schedules. Residents in one university-based training program provided preliminary interpretations of 18,488 overnight (11 pm–8 am) studies at a level 1 trauma center between July 1, 2013 and December 31, 2014. As part of their normal workflow and feedback, attendings scored the reports as major discrepancy, minor discrepancy, agree, and agree--good job. We retrospectively obtained the preliminary interpretation scores for each study. Total relative value units (RVUs) per shift were calculated as an indicator of overnight workload. The dataset was supplemented with information on trainee level, number of consecutive nights on night float, hour, modality, and per-shift RVU. The data were analyzed with proportional logistic regression and Fisher's exact test. There were 233 major discrepancies (1.26 %). Trainee level (senior vs. junior residents; 1.08 vs. 1.38 %; p < 0.05) and modality were significantly associated with performance. Increased workload affected more junior residents' performance, with R3 residents performing significantly worse on busier nights. Hour of the night was not significantly associated with performance, but there was a trend toward best performance at 2 am, with subsequent decreased accuracy throughout the remaining shift hours. Improved performance occurred after the first six night float shifts, presumably as residents acclimated to a night schedule. As overnight shift work schedules increase in popularity for residents and attendings, focused attention to factors impacting interpretative accuracy is warranted.