Sparse information exists about chronic obstructive pulmonary disease (COPD) outcomes among different ethnic groups. To determine whether the effect of tiotropium on COPD exacerbation differs between African Americans and Caucasians, we performed a post hoc analysis of African-American (n = 150) and Caucasian (n = 1670) subgroups from a previously reported 6-month trial of tiotropium in patients with moderate-to-very-severe COPD. Compared with placebo, tiotropium reduced the likelihood of having at least 1 exacerbation in the entire group (RR, 0.81; 95% CI, 0.66-0.99, P = 0.037) with no statistically significant difference between African-American and Caucasian subgroups (P = 0.34). For African Americans, tiotropium significantly reduced the number of antibiotic days for COPD, hospitalizations for exacerbations, and hospitalization days for COPD. For Caucasians, tiotropium significantly reduced the number of exacerbations, exacerbation days, unscheduled clinic visits for COPD, and hospitalizations for exacerbations. Tiotropium reduced the frequencies of antibiotic days and of COPD hospital days to a significantly greater extent in African Americans compared with Caucasians (P = 0.027 and P = 0.025, respectively). No statistically significant ethnic-related differences were observed in the effect of tiotropium on the frequencies of exacerbations, exacerbation days, systemic corticosteroid days, unscheduled clinic visits, or COPD hospitalizations. Spirometry improved to a similar extent in both subgroups for the entire duration of the 6-month trial. African Americans used fewer respiratory medications than Caucasians in this study. We conclude that tiotropium reduces COPD exacerbations and associated health-care use to a similar extent in African Americans compared with Caucasians.