<jats:p> <jats:italic>Background</jats:italic> —PTCA is performed primarily to improve health-related quality of life (HRQOL) in patients with symptomatic coronary artery disease. In patients undergoing PTCA, smoking has been shown to increase risks of late myocardial infarction and death. Whether smoking also affects HRQOL after PTCA is currently unknown. </jats:p> <jats:p> <jats:italic>Methods and Results</jats:italic> —We examined the relation between smoking status and HRQOL among 1432 patients who underwent PTCA as part of 2 multicenter clinical trials. HRQOL was assessed with the use of the Medical Outcomes Study SF-36 questionnaire. Patients were classified as smokers (n=301), quitters (n=141), or nonsmokers (n=990) on the basis of their smoking status at the time of their index procedure and during the first year of follow-up. For the overall population, HRQOL improved significantly after PTCA for all scales except general health perception, with improvements ranging from 5.5 points for mental health to 23.2 points for role-physical functioning. After adjustment for baseline characteristics and initial HRQOL, nonsmokers had gains at 6 months that were larger than those of smokers for all health domains: physical function (15.4 versus 10.4 points), role-physical (24.5 versus 13.9), pain (18.4 versus 13.3), general health perception (1.7 versus −4.5), vitality (11.0 versus 4.7), social function (12.8 versus 3.5), role-emotional (13.5 versus 6.7), and mental health (6.8 versus 0.8; <jats:italic>P</jats:italic> <0.02 for all comparisons). Quitters had 6-month HRQOL improvements that were greater than those in smokers for all domains as well. Findings were similar at 1 year. </jats:p> <jats:p> <jats:italic>Conclusions</jats:italic> —Quality-of-life benefits of PTCA are diminished by continued smoking. Efforts to promote smoking cessation at the time of PTCA may substantially improve the health outcomes of these procedures. </jats:p>