The relationship between educational outcomes and the use of web-based clinical knowledge support systems in teaching hospitals remains unknown in Japan. A previous study on this topic could have been affected by recall bias because of the use of a self-reported questionnaire. We aimed to explore the relationship between the use of the Wolters Kluwer UpToDate clinical knowledge support system in teaching hospitals and residents' General Medicine In-Training Examination (GM-ITE) scores. In this study, we objectively evaluated the relationship between the total number of UpToDate hospital use logs and the GM-ITE scores. This nationwide cross-sectional study included postgraduate year-1 and -2 residents who had taken the examination in the 2020 academic year. Hospital-level information was obtained from published web pages, and UpToDate hospital use logs were provided by Wolters Kluwer. We evaluated the relationship between the total number of UpToDate hospital use logs and residents' GM-ITE scores. We analyzed 215 teaching hospitals with at least 5 GM-ITE examinees and hospital use logs from 2017 to 2019. The study population consisted of 3013 residents from 215 teaching hospitals with at least 5 GM-ITE examinees and web-based resource use log data from 2017 to 2019. High-use hospital residents had significantly higher GM-ITE scores than low-use hospital residents (mean 26.9, SD 2.0 vs mean 26.2, SD 2.3; P=.009; Cohen d=0.35, 95% CI 0.08-0.62). The GM-ITE scores were significantly correlated with the total number of hospital use logs (Pearson r=0.28; P<.001). The multilevel analysis revealed a positive association between the total number of logs divided by the number of hospital physicians and the GM-ITE scores (estimated coefficient=0.36, 95% CI 0.14-0.59; P=.001). The findings suggest that the development of residents' clinical reasoning abilities through UpToDate is associated with high GM-ITE scores. Thus, higher use of UpToDate may lead physicians and residents in high-use hospitals to increase the implementation of evidence-based medicine, leading to high educational outcomes.