Objectives: We sought to determine the relationship between cigarette smoking and outcomes after mechanical reperfusion therapy in acute myocardial infarction(AMI). Background: Prior studies have found that smokers with AMI have lower mortality rates and a more favorable response to fibrinolytic therapy than nonsmokers. The impact of cigarette smoking in patients undergoing primary percutaneous coronary intervention has not been examined. Methods: In the CADILLAC trial, 2082 patients with AMI were randomized to percutaneous transluminal coronary angioplasty±abciximab versus stenting±abciximab. Data on smoking status were prospectively collected and follow-up continued for 1 year. Results: At the time of presentation, 638(31%) patients had never smoked, 546(26%) were former smokers, and 898(45%) were currently smoking. In comparison to nonsmokers, current smokers were younger, more often men, and less frequently had diabetes, hypertension, prior AMI, and triple-vessel coronary disease. Procedural success rates were unrelated to smoking status. Mortality was lowest in current smokers, intermediate in former smokers, and highest in nonsmokers at 30 days(1.3%vs 1.7%vs 3.5%, respectively, P=.02) and 1 year(2.9%vs 3.7%vs 6.6%, P=.0008). After multivariate correction for differences in baseline variables, however, current smoking status was no longer protective from late mortality(hazard ratio 0.96, 95%CI 0.52-1.76, P=.89). Conclusions: The “smokers paradox”extends to patients undergoing primary PCI for AMI, with increased survival seen in current smokers, an effect entirely explained by differences in baseline risk and not smoking status per se. The deleterious effects of smoking are expressed in the occurrence of AMI nearly a decade earlier than in nonsmokers, with similar age-adjusted risk, mandating intensive primary and secondary cigarette-cessation efforts. Objectives: We sought to determine the relationship between cigarette smoking and outcomes after mechanical reperfusion therapy in acute myocardial infarction (AMI). Background: Prior studies have found that smokers with AMI have lower mortality rates and a more favorable response to fibrinolytic therapy than nonsmokers. The impact of cigarette smoking in patients undergoing primary percutaneous coronary intervention has not been examined. Methods: In the CADILLAC trial, 2082 patients with AMI were randomized to percutaneous transluminal coronary angioplasty ± abciximab versus stenting ± abciximab. Data on smoking status were prospectively collected and Follow-up continued for 1 year. Results: At the time of presentation, 638 (31%) patients had never smoked, 546 (26%) were former smokers, and 898 (45%) were currently smoking. current smokers were younger, more often men, and less frequently had diabetes, hypertension, prior AMI, and triple-vessel coronary disease . Procedural success rates were unrelated to smoking status. Mortality was lowest in current smokers, intermediate in former smokers, and highest in nonsmokers at 30 days (1.3% vs 1.7% vs 3.5%, respectively, P = .02) and 1 year ( 2.9% vs 3.7% vs 6.6%, P = .0008). After multivariate correction for differences in baseline variables, however, current smoking status was no longer protective from late mortality (hazard ratio 0.96, 95% CI 0.52-1.76, P = .89). Conclusions: The “smoker’s paradox” extends to patients undergoing primary PCI for AMI, with increased survival seen in current smokers, an effect entirely explained by differences in baseline risk and not smoking status per se. The deleterious effects of smoking are expressed in the occurrence of AMI nearly a decade earlier than in nonsmokers, with similar age-adjusted risk, mandating intensive primary and secondary cigarette-cessation efforts.