We sought to determine the incidence, clinical features, and risk factors for retroperitoneal hematoma (RPH) after percutaneous coronary intervention (PCI). Little is known about the clinical features, outcomes, and determinants of this serious complication in the contemporary era of PCI. A retrospective analysis yielded 26 cases of RPH out of 3,508 consecutive patients undergoing PCI between January 2000 and January 2004. Cases were compared with a randomly selected sample of 50 control subjects without RPH. The incidence of RPH was 0.74%. Features of RPH included abdominal pain (42%), groin pain (46%), back pain (23%), diaphoresis (58%), bradycardia (31%), and hypotension (92%). The mean systolic blood pressure nadir was 75 mm Hg. The hematocrit dropped by 11.5 +/- 5.1 points from baseline in RPH patients, as compared with 2.3 +/- 3.3 points in controls (p < 0.0001). The mean hospital stay was longer in RPH patients (2.9 +/- 3.8 days vs. 1.7 +/- 1.5 days, p = 0.06). The following variables were found to be independent predictors of RPH: female gender (odds ratio [OR] 5.4, p = 0.005), low body surface area (BSA <1.73 m(2); OR 7.1, p = 0.008), and higher femoral artery puncture (OR 5.3, p = 0.013). There was no association between RPH and arterial sheath size, use of glycoprotein IIb/IIIa inhibitors, or deployment of a vascular closure device. Female gender, low BSA, and higher femoral artery puncture are significant risk factors for RPH. Awareness of the determinants and clinical features of RPH may aid in prevention, early recognition, and prompt treatment.