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Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability globally. Both cigarette smoking and HIV have been identified as independent risk factors for COPD. We used data from the strategic timing of antiretroviral treatment (START) Pulmonary Substudy to quantify the impact of smoking on rate of lung function decline in HIV.We included START Pulmonary Substudy participants who contributed at least 2 good quality spirometry measures during the study. Slope of forced expiratory volume in 1 second (FEV1) was estimated using a repeated-measures model adjusted for the treatment group (immediate vs deferred treatment arm of START), age, sex, race, baseline COPD, and region.Of 1026 START Pulmonary Substudy participants, 915 (89%) were included in this analysis. Median follow-up time was 3.9 years. Smokers and nonsmokers were similar in baseline age (median 36 years), but smokers were more likely to be white, male, and from Europe/Israel/Australia. Smokers had faster average FEV1 decline compared with nonsmokers [−38.3 mL/yr vs −25.1 mL/yr; difference of −13.2 mL/yr (95% confidence interval: −23.6 to −2.7); P = 0.013], were more likely to meet criteria for rapid FEV1 decline [7.2%–11.7% more likely (P = 0.09–P = 0.002), depending on the definition of rapid decline], and had borderline, but not statistically significant, higher incident COPD during follow-up (9.7% vs 5.8%, P = 0.06).Compared to nonsmokers, HIV-positive smokers experience faster decline in lung function. These results underscore the need for a better understanding of how to best support smoking cessation among HIV-positive populations.