Objectives. We sought to determine smoklng-related hazard ratios (HRs) and population-attributable risk percentage (PAR%) for serious clinical events and death among HIV-positive persons, whose smoking prevalence is higher than In the generai population. Methods. For 5472 HIV-infected persons enrolled from 33 countries in the Strategies for Management of Antiretroviral Therapy clinical trial, we evaluated the relationship between baseline smoking status and development of AIDSrelated or serious non-AIDS events and overall mortality. Results. Among all participants, 40.5% were current smokers and 24.8% were former smokers. Adjusted HRs were higher for current than for never smokers for overall mortality (2.4; P<.001), major cardiovascular disease (2.0; P=,002), non-AIDS cancer (1.8; P= .008), and bacterial pneumonia (2.3; P<.001). Adjusted HRs also were significantly higher for these outcomes among current than among former smokers. The PAR% for current versus former and never smokers combined was 24.3% for overall mortality, 25.3% for major cardiovascular disease, 30.6% for non-AIDS cancer, and 25.4% for bacterial pneumonia. Conclusions. Smoking contributes to substantial morbidity and mortality in this HIV-infected population. Providers should routinely integrate smoking cessation programs into HIV health care.