Aim To determine whether changes in the format of teaching pathology and the introduction of active learning principles can improve medical students' performance on external examinations and enhance clinical skills. Method The sophomore Pathology Course at Jefferson Medical College (JMC) in Philadelphia, Pennsylvania, USA, was completely restructured in 1986, with greater emphasis placed on independent study, small group teaching, and case study discussion. We used the scores of JMC medical students on the National Board of Medical Examiners (NBME) Part I Examination to compare the performance of JMC students who completed their medical education before curricular change (entering classes 1982-1984) with the performance of subsequent generations of students who were taught according to the reformed curriculum (entering classes 1985-1988). Results The two groups of students were comparable in terms of standard social and psychometric parameters, such as mean age at matriculation, female/male ratio, ratio of minority students in the class, premedical college grade point averages, and mean scores on the preadmission Medical College Admissions Test. JMC students who studied pathology prior to the curricular reform received on the pathology subsection of the NBME Part I Examination reform scores that were close to the national average. In contrast, mean scores for students who studied pathology after curricular changes were significantly higher than the national average (P < 0.001). Based on their pathology subscores, the number of JMC students scoring below the cutoff line for passing (380 points) decreased significantly after the curricular reform, whereas the number of high-scoring students whose scores ranked them in the 90th percentile nationally increased. Curricular reform was also associated with an increase in overall student satisfaction. Conclusion Curricular changes that include an emphasis on active learning can improve the performance of medical students on externally administered, objective examinations. We have shown that the means of the medical school class can be improved, the number of failing students reduced, and the number of high-scoring students increased. The improvement of students' scores was not limited to the first class after curricular reform, but persisted throughout the entire observation period of four years.