The reported complication rate of catheter ablation of atrial fibrillation (AF) varies. Our goal was to assess temporal trends and the effect of both institutional and individual operators' experience on the incidence of complications. All patients undergoing AF ablation at Johns Hopkins Hospital between February 2001 and December 2010 were prospectively enrolled in a database. Major complications were defined as those that were life-threatening, resulted in permanent harm, required intervention, or significantly prolonged hospitalization. Fifty-six major complications occurred in 1190 procedures (4.7%). The majority of complications were vascular (18; 1.5%), followed by pericardial tamponade (13; 1.1%) and cerebrovascular accident (12; 1.1%). No cases of death or atrioesophageal fistula occurred. The overall complication rate decreased from 11.1% in 2002 to 1.6% in 2010 (P <.05). On univariate analysis, demographic and clinical factors associated with the increased risk of complications were CHADS(2) score of ≥2 (hazard ratio HR = 2.5; 95% confidence interval CI = 1.4-4.4; P = .002), female gender (HR = 2.0; 95% CI = 1.2-3.5; P = .014), and age (HR = 1.03; 95% CI = 1.0-1.1; P = .042). Gender and CHADS(2) score of ≥2 remained independent predictors of complication on multivariable analysis. The complication rate of catheter ablation of AF decreased with increased institutional experience. Female gender and CHADS(2) score of ≥2 are significant independent risk factors for complications and should be considered when referring patients for AF ablation.