Background: Kidney dysfunction (KD) has been associated with increased risk for major bleeding (MB) in patients with acute coronary syndromes (ACS) and may be in part related to an underuse of evidence-based therapies. Our aim was to assess the predictive ability of the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) risk score in patients with concomitant ACS and chronic kidney disease. Methods: We conducted a retrospective analysis of a prospective registry including 1,587 ACS patients. In-hospital MB was prospectively recorded according to the CRUSADE and Bleeding Academic Research Consortium (BARC) criteria. KD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. Results: The predictive ability of the CRUSADE risk score was assessed by discrimination and calibration analyses. A total of 465 (29%) subjects had KD. In multivariate logistic regression analyses, we found high CRUSADE risk score values to be associated with a higher rate of in-hospital MB; however, among patients with KD, it was not associated with BARC MB. Regardless of the MB definition, the predictive ability of the CRUSADE score in patients with KD was lower: area under the curve (AUC) 0.71 versus 0.79, p = 0.03 for CRUSADE MB and AUC 0.65 versus 0.75, p = 0.02 for BARC MB. Hosmer-Lemeshow analyses showed a good calibration in all renal function subgroups for both MB definitions (all p values >0.3). Conclusions: The CRUSADE risk score shows a lower accuracy for predicting in-hospital MB in KD patients compared to those without KD.