Objectives: To investigate if previously reported gender-based outcome disparities following percutaneous coronary intervention (PCI) are applicable in a large and racially-diverse cohort in the drug eluting stent (DES) era. Background: It is generally believed that women suffer inferior outcomes compared to men after PCI. However, various strategies have evolved that may have mitigated this imbalance, including improved medical therapy, attention to risk-factors, and procedural advances of PCI including DES. Methods: We identified 13,752 patients (4,761 female, 34.6%) with complete follow-up data who underwent de novo lesion PCI from 04/2003 to 04/2009. Relevant data were extracted from an IRB-approved registry. Results: Compared to males, females were significantly older (69.0 vs. 64.8 years) and more frequently from a minority or non-Caucasian background. Females smoked less, but more were hypertensive and/or diabetic. Women had higher HDL, but also higher LDL cholesterol levels. More women presented with an unstable coronary syndrome and required left anterior descending artery PCI. While unadjusted post-PCI mortality rates were higher in females versus males (30 days, 1.3 vs. 0.8%, P = 0.009; 1 year, 6.1 vs. 4.8%, P = 0.001; 3 year, 10.4 vs. 8.4%, P < 0.0001), multivariable regression analyses failed to identify female gender as an independent predictor of mortality. Propensity-adjusted modeling confirmed that females were not at intrinsically higher risk for mortality after PCI. Conclusions: Females undergoing PCI exhibit more comorbidities and adverse prognostic factors than males. However, risk-adjusted analyses identified that gender is not an independent predictor of mortality after PCI in the DES era. © 2011 Wiley Periodicals, Inc.