Background: Clinical trials provide limited information about the outcome of patients with acute coronary syndromes (ACSs) and kidney disease (KD) owing to underrepresentation of this population in most studies. Methods: To evaluate the outcome of patients with non-ST-segment elevation ACS (NSTE-ACS) and KD in a real-world setting, we compared the risk of in-hospital and 30-day mortality by the presence of KD (defined as an estimated glomerular filtration rate <60mL/min/1.73m2) in 13 141 patients with NSTE-ACS enrolled in 3 multinational ACS registries between 2000 and 2006 as part of the European Public Health Outcome Research and Indicators Collection Project. Results: Patients with KD (n=4181) composed 31.8% of the study population and had significantly higher rates of in-hospital (5.4%) and 30-day (7.2%) case fatality compared with patients without KD (1.1% and 1.7%, respectively; P<.001 for both). In multivariate analysis, the presence of KD was independently associated with a significantly higher mortality risk (in-hospital: odds ratio [OR], 2.11; 95% confidence interval [CI], 1.48-3.00; 30-day: OR, 1.95; 95% CI, 1.46-2.61). Patients with KD who underwent coronary angiography experienced a 36% (P=.05) and 40% (P<.001) lower risk of in-hospital and 30-day mortality, respectively, but this high-risk population still exhibited significantly higher case-fatality rates during hospitalization (3.3%) and at 30 days (4.6%) compared with patients without KD who underwent coronary angiography (0.7% and 1.3%, respectively; P<.001 for all). Conclusions: In a real-world setting, KD was present in approximately one-third of patients with NSTE-ACS and is a powerful independent predictor of subsequent mortality. Patients with NSTE-ACS and KD referred for coronary angiography have a significantly lower risk of death, but this high-risk population continues to exhibit increased mortality rates despite intervention procedures.