The epidemiology of tuberculin reactivity among physicians practicing in regions of moderate tuberculosis prevalence is unknown. We prospectively assessed the epidemiology of tuberculin skin test (TST) reactivity among physicians in training in St. Louis between 1992 and 1998. Of 1574 physicians who were tested, 267 (17%) had positive TST results. Older age, birth outside of the United States, prior bacille Calmette-Guérin (BCG) vaccination, and practice in the fields of medicine, anesthesiology, or psychiatry were associated with a positive TST result. Among physicians born in the United States, 63 (5.7%) had positive TST results. Among physicians with ≥2 documented TSTs, 12 had conversion to a positive TST (1.6%; 1.03 conversions per 100 person-years). Physicians in this study had a high rate of tuberculin reactivity, despite a low conversion rate. The relationship between TST conversion and birth outside of the United States and BCG vaccination suggests a booster phenomenon rather than true new TST conversions.