Cardiorenal syndrome type 1 (CRS1), defined as worsening renal function from acute decompensated congestive heart failure (ADCHF), is complicated by the fact that CRS1 limits the use of common therapeutic strategies, such as angiotensin converting-enzyme inhibitors (ACEIs) or angiotensin II-receptor blockers (A2RB). The present study examines retrospectively the role of ACEI/A2RB usage on in-hospital mortality among elderly ADCHF patients, in particular those who developed CRS1. Methods: We retrospectively examined the effects of ACEI/A2RB usage and CRS1 development (in-hospital change in serum creatinine ≥0.3 mg/dL or ≥0.5 mg/dL), as well as their potential interaction, on in-hospital mortality among elderly ADCHF patients (aged ≥65 years). Employing univariate and multivariate analyses, we performed risk-factor analysis on a cohort of 419 patients (51 nonsurvivors [12.2%]) for whom we had complete clinical and laboratory data (median follow-up 5 days) from 2,361 consecutive elderly ADCHF patients (106 nonsurvivors [4.6%]). Results: By multivariate analysis, the two strongest independent predictors of in-hospital mortality were CRS1 development (OR 7.8, 95% CI 3.9-15.5; P=0.00001) and lack of ACEI/A2RB usage (OR 0.49, CI 0.25-0.93; P=0.043). The effect of CRS1 was graded, with increasing CRS1 severity associated with increased mortality. On multivariate subgroup analysis, the association between lack of ACEI/A2RB usage and increased mortality remained a significant independent predictor among patients not developing CRS1 (OR 0.24, CI 0.083-0.721; P=0.011). Conclusion: Our data suggest that development of CRS1 and lack of ACEI/A2RB usage are statistically independent predictors of in-hospital mortality for elderly ADCHF patients, with CRS1 being the stronger of the two risk factors. While it remains unclear whether lack of ACEI/ A2RB usage is causally related to increased mortality or reflects another risk factor inducing physicians to forego ACEIs/A2RBs, our findings nevertheless indicate the need to address this issue in future prospective studies.