Objective Although several studies have been conducted worldwide on factors that might improve residents' knowledge, the relationship between the hospital volume and the internal medicine residents' knowledge has not been fully understood. We conducted a cross-sectional study to compare the relationships of the hospital volume and hospital resources with the residents' knowledge assessed by the In-training Examination. Methods We conducted a retrospective survey and a clinical knowledge evaluation of postgraduate year 1 and 2 (PGY-1 and -2) resident physicians in Japan by using the General Medicine In-training Examination (GM-ITE) in 2014. We compared the ITE score and the hospital volume. Results A total of 2,015 participants (70.6% men; age, 27.3±2.9 years old) from 208 hospitals were retrospectively analyzed. Generalized estimating equations were used, and the results revealed that an increasing number of hospitalizations, decreasing staff number, decreasing age and PGY-2 were significantly associated with higher GM-ITE scores. Conclusion The hospital volume, such as the number of hospitalizations, is thus considered to have a positive impact on the GM-ITE scores.