In-hospital cardiac arrest (IHCA) is common and is associated with poor prognosis. Data on the effect of smoking on outcomes after IHCA are limited. We analyzed the Nationwide Inpatient Sample databases from 2003 to 2011 for all patients aged ≥18 years who underwent cardiopulmonary resuscitation (CPR) for IHCA to examine the differences in survival to hospital discharge and neurologic status between smokers and nonsmokers. Of the 838,464 patients with CPR for IHCA, 116,569 patients (13.9%) were smokers. Smokers were more likely to be younger, Caucasian, and male. They had a greater prevalence of dyslipidemia, coronary artery disease, hypertension, chronic pulmonary disease, obesity, and peripheral vascular disease. Atrial fibrillation, heart failure, and diabetes mellitus with complications were less prevalent in smokers. Smokers were more likely to have a primary diagnosis of acute myocardial infarction (14.8% vs 9.1%, p <0.001) and ventricular tachycardia or ventricular fibrillation as the initial cardiac arrest rhythm (24.3% vs 20.5%, p <0.001). Smokers had a higher rate of survival to hospital discharge compared with nonsmokers (28.2% vs 24.1%, adjusted odds ratio 1.06, 95% confidence interval 1.05 to 1.08, p <0.001). Smokers were less likely to have a poor neurologic status after IHCA compared with nonsmokers (3.5% vs 3.9%, adjusted odds ratio 0.92, 95% confidence interval 0.89 to 0.95, p <0.001). In conclusion, among patients aged ≥18 years who underwent CPR for IHCA, we observed a higher rate of survival in smokers than nonsmokers—consistent with the “smoker's paradox.” Smokers were also less likely to have a poor neurologic status after IHCA.