BackgroundSmoker's paradox usually refers to the observation of a favorable outcome of smoking patients in acute myocardial infarction. MethodsFrom April 2006 to December 2018 a population of 2456 patients with ST segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI) were prospectively enrolled in the MATRIX registry. Ischemic time, clinical, demographics, angiographic data, and 1-year follow-up were collected. ResultsAmong 2546 patients admitted with STEMI, 1007 (41 %) were current smokers. Smokers were 10 years younger and had lower crude in-hospital and 1-year mortality (1.5 % vs 6 %, p < 0.0001 and 5 % vs 11 %, p < 0.0001), shorter ischemic time (203 [147–299] vs 220 [154–334] minutes, p = 0.002) and shorter decision time (60 [30–135] vs 70 [36–170] minutes, p = 0.0063). Smoking habit [OR:0.37(95 % CI:0.18–0.75)-p < 0.01], younger age [OR 1.06 (95%CI:1.04–1.09)-p < 0.001] and shorter ischemic time [OR:1.01(95%CI:1.01–1.02)-p < 0.05] were associated to lower in-hospital mortality. Only smoking habit [HR:0.65(95 % CI: 0.44–0.9)–p = 0.03] and younger age [HR:1.08 (95%CI:1.06–1.09)–p < 0.001] were also independently associated to lower all-cause death at 1-year follow-up. After propensity matching, age, cardiogenic shock and TIMI flow <3 were associated with in-hospital mortality, while smoking habit was still associated with reduced mortality. Smoking was also associated with reduced mortality at 1-year follow-up (HR 0.54, 95 % CI [0.37–0.78]; p < 0.001). ConclusionsSmoking patients show better outcome after PCI for STEMI at 1-year follow-up. Although “Smoking paradox” could be explained by younger age of patients, other factors may have a role in the explanation of the phenomenon.