The effect of heart failure drugs on mortality in patients with high or low serum creatinine levels has not been well studied. Available trials with counts of mortality by placebo or treatment separated by median serum creatinine (mol/l) levels were used to construct dichotomous datasets for each drug. ACE inhibitor studies were: SOLVD (n = 6655, % mortality for placebo and treatment are: for <120 umol/l 5% vs. 4% and for ≥120mol/l 9% vs. 7%) and CONSENSUS (n = 2289, for <120mol/l 38% vs. 24% and for ≥120mol/l 50% vs. 29%). Beta-blockers studied were: CIBIS II (n = 2647, for < 6 ml/min 23% vs. 15% and for ≥6 ml/min 14% vs. 10%) and COPERNICUS (n = 2286, for <125mol/l 13% vs. 8% and for ≥125mol/l 20% vs. 14%). All variables were significant at p = 0.00 in the ACEi analysis. ACEi treatment (OR = 0.72; 95% CI: 0.60–0.86) was protective against mortality. High creatinine (OR = 1.80; 95% CI: 1.50–2.16) was not protective against mortality. Enalapril worked more effectively on patients with high creatinine compared to low creatinine in preventing mortality (OR = 0.54; 95% CI: 0.41–0.72). Beta-blockers (BB) were protective against mortality (OR = 0.6, p = 0.00; 95% CI: 0.46–0.77). In CIBIS II and COPERNICUS those with high creatinine were not worse off in terms of mortality (OR = 0.93, p = 0.50; 95% CI: 0.75–1.15). BB did not have a differential effect on mortality by creatinine group (OR = 1.1, p = 0.59; 95% CI: 0.79–1.52).