Context. - The Department of Pathology of the Johns Hopkins University pioneered in the late 19th century the application of the scientific method to the study of medicine and fostered the development of residency training programs. Objective. - To trace the history of the Johns Hopkins Pathology Residency Program and assess with quantifiable outcomes the performance of former residents. Design. - We reviewed archival and departmental records from September 1899 to June 2014 to create a database of pathology residents. We then analyzed resident in-service examinations, American Board of Pathology examinations, and career paths. Results. - In 115 years the department trained 555 residents who came from 133 medical schools located in 23 countries. Residents performed well on the in-service examinations, obtaining mean scaled total scores that were significantly better (P = .02) than those of the national peer groups. Residents (371 of 396, 94%) passed their boards typically at the first attempt, a percentage pass that was higher than the national average for both anatomic (P < .001) and clinical (P = .002) pathology. Approximately half of the residents went into private practice, whereas a third followed an academic career. Of the latter group, 124 (75%) became professors of pathology, 31 (19%) chairs of pathology departments, 10 (6%) deans of medical schools, 5 (3%) were elected into the National Academy of Sciences, and 1 won the Nobel prize. Conclusions. - While maintaining its original core values, the Johns Hopkins Pathology Residency Program has trained physicians to be outstanding researchers, diagnosticians, and leaders in pathology.