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Background\ud Prior studies have reported inconsistencies in the baseline risk profile, comorbidity burden and their association with clinical outcomes in women compared to men. More importantly, there is limited data around the sex differences and how these have changed over time in contemporary percutaneous coronary intervention (PCI) practice.\ud \ud Methods and results\ud We used the Nationwide Inpatient Sample to identify all PCI procedures based on ICD-9 procedure codes in the United States between 2004–2014 in adult patients. Descriptive statistics were used to describe sex-based differences in baseline characteristics and comorbidity burden of patients. Multivariable logistic regressions were used to investigate the association between these differences and in-hospital mortality, complications, length of stay and total hospital charges. Among 6,601,526 patients, 66% were men and 33% were women. Women were more likely to be admitted with diagnosis of NSTEMI (non-ST elevation acute myocardial infarction), were on average 5 years older (median age 68 compared to 63) and had higher burden of comorbidity defined by Charlson score ≥3. Women also had higher in-hospital crude mortality (2.0% vs 1.4%) and any complications compared to men (11.1% vs 7.0%). These trends persisted in our adjusted analyses where women had a significant increase in the odds of in-hospital mortality men (OR 1.20 (95% CI 1.16,1.23) and major bleeding (OR 1.81 (95% CI 1.77,1.86).\ud \ud Conclusion\ud In this national unselected contemporary PCI cohort, there are significant sex-based differences in presentation, baseline characteristics and comorbidity burden. These differences do not fully account for the higher in-hospital mortality and procedural complications observed in women.