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Smoking is common in patients with HIV and is associated with increased morbidity and mortality. With the goal of targeting future cessation interventions, we sought to identify factors associated with smoking status, readiness and confidence in cessation, and success in quitting. As part of a larger study in New York City assessing predictors of chronic obstructive pulmonary disease (COPD), we enrolled HIV-infected subjects at least 35 years of age without known asthma or COPD. Current smokers received detailed tobacco history, and smoking status was assessed by chart review at 3 and 6 months post-enrollment. Two hundred subjects were enrolled (29% current smokers, 31.5% never smokers, 39.5% former smokers, mean age of 49, 84% male, 64% had AIDS, and 97% were receiving antiretroviral therapy). Current smokers had higher unemployment and increased rates of other substance use than former smokers or never smokers. In multivariate analysis, being unemployed and having used inhalant drugs were associated with current smoking. Substance abuse history was not correlated with readiness to quit or patient estimated cessation. Lower education was associated with decreased readiness to quit. Follow-up smoking status for baseline current smokers was available for 47/58 enrollees at 6 months; 4 (9%) stopped smoking completely, and 17 (36%) decreased the number of packs-per-day. Smoking and concomitant substance abuse is common in HIV, and special attention should be given to this issue, in addition to a patient's readiness to quit, when implementing tobacco cessation protocols, especially in busy urban HIV care centers.