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Despite the prevalence of musculoskeletal disorders, the degree to which medical schools are providing students with the knowledge and confidence to treat these problems is unclear. This study evaluated the factors that impact musculoskeletal knowledge and clinical confidence among fourth-year medical students.Over a three-year period, 253 fourth-year medical students participated in the study at a single institution. Musculoskeletal knowledge was evaluated using a National Board of Medical Examiners’ musculoskeletal medicine subject examination. Factors analyzed included sex, class year, musculoskeletal elective experience, duration of musculoskeletal elective, career choice, and musculoskeletal curriculum satisfaction.The participation rate was 95%. The mean National Board of Medical Examiners’ musculoskeletal assessment score (and standard deviation) was 70.7 ± 9.5 points for all fourth-year medical students. Taking a musculoskeletal elective significantly increased knowledge (p < 0.001) but not clinical confidence. Increased satisfaction with how musculoskeletal medicine was taught was associated with increased clinical confidence (p < 0.001). No significant differences were seen if students were going into musculoskeletal medicine or primary care for either musculoskeletal knowledge or clinical confidence. Multivariate analysis of musculoskeletal knowledge found that taking a musculoskeletal elective for two weeks led to an increase of 6 points (from a possible 100 points) in the National Board of Medical Examiners’ subject examination scores.This study reveals that participation in a clinical elective is the only factor that led to a significant increase in musculoskeletal knowledge in fourth-year medical students. A two-week clinical elective can be sufficient time to have an impact on musculoskeletal knowledge, but it alone does not increase clinical confidence. Further studies are needed to determine how to improve musculoskeletal clinical confidence.