Purpose: Despite the prevalence of musculoskeletal (MSK) disorders, the degree to which medical schools are providing students the knowledge and confidence to treat these problems is unclear. This study evaluated MSK knowledge in second and fourth year medical students using a newly developed written assessment tool and examined the maturation of clinical confidence in treating core MSK disorders. Methods: Over a 3-year period, the National Board of Medical Examiners (NBME) MSK subject examination consisting of 75 items was administered to 568 second and fourth year students at a single institution. Students were also asked to rate their confidence in treating a selection of medicine/pediatric and MSK clinical scenarios on a 5-point Likert scale. Results: Participation rate was 98%. The NBME MSK assessment score was 59.2±10.6 for all second year medical students and 69.7±9.6 for all fourth year medical students. There was a significant increase in NBME scores between the second and fourth years (p<0.0001). Students were more confident in treating internal medicine/pediatric conditions than MSK medicine conditions (p=0.001). Confidence in treating MSK medicine conditions did not improve between the second and fourth years (p=0.41). Conclusions: To our knowledge, this is the first study to report increased MSK medicine knowledge as measured by a standardized examination after completing medical school core clinical rotations. Despite increased MSK knowledge, low levels of MSK clinical confidence among graduating students were noted. Further research is needed to determine the factors that influence MSK knowledge and clinical confidence in medical students.