Several microlevel studies have pinpointed prisons as an important site for tuberculosis (TB) and multidrug-resistant TB in European and central Asian countries. To date, no comparative analyses have examined whether rises in incarceration rates can account for puzzling differences in TB trends among overall populations. Using longitudinal TB and cross-sectional multidrug-resistant TB data for 26 eastern European and central Asian countries, we examined whether and to what degree increases in incarceration account for differences in population TB and multidrug-resistant TB burdens. We find that each percentage point increase in incarceration rates relates to an increased TB incidence of 0.34% (population attributable risk, 95% C.I.: 0.10-0.58%, P < 0.01), after controlling for TB infrastructure; HIV prevalence; and several surveillance, economic, demographic, and political indicators. Net increases in incarceration account for a 20.5% increase in TB incidence or nearly three-fifths of the average total increase in TB incidence in the countries studied from 1991 to 2002. Although the number of prisoners is a significant determinant of differences in TB incidence and multidrug-resistant TB prevalence among countries, the rate of prison growth is a larger determinant of these outcomes, and its effect is exacerbated but not confounded by HIV. Differences in incarceration rates are a major determinant of differences in population TB outcomes among eastern European and central Asian countries, and treatment expansion alone does not appear to resolve the effect of mass incarceration on TB incidence.