The association between corticosteroid therapy and subsequent infections was calculated by pooling data from 71 controlled clinical trials. The overall rate of infectious complications was 12.7% in the 2,111 patients randomly allocated to systemic corticosteroids and 8.0% in the 2,087 controls (relative risk [RR], 1.6; 95% confidence interval [CI], 1.3–1.9; P < .001). The risk of infection was particularly high in patients with neurologic diseases (RR, 2.8; 95% CI, 1.9–4.3; P< .001) and less pronounced in patients with intestinal (RR, 1.4; 95% CI, 1.1–1.7; P = .02), hepatic (RR, 1.4; 95% CI, 0.9–2.3; P = .25), and renal (RR>1; P = .03) diseases. The rate was not increased in patients given a daily dose of <10 mg or a cumulative dose of <700 mg of prednisone. With increasing doses the rate of occurrence of infectious complications increased in patients given corticosteroids as well as in patients given placebo, a finding suggesting that not only the corticosteroid but also the underlying disease state account for the steroid-associated infectious complications observed in clinical practice.