Background: Compared with serum potassium levels 4-5.5-mEq/L, those < 4-mEq/L have been shown to increase mortality in chronic heart failure (HF). Expert opinions suggest that serum potassium levels > 5.5-mEq/L may be harmful in HF. However, little is known about the safety of serum potassium 5-5.5-mEq/L. Methods: Of the 7788 chronic HF patients in the Digitalis Investigation Group trial, 5656 had serum potassium 4-5.5-mEq/L. Of these, 567 had mild hyperkalemia (5-5.5-mEq/L) and 5089 had normokalemia (4-4.9-mEq/L). Propensity scores for mild hyperkalemia were used to assemble a balanced cohort of 548 patients with mild hyperkalemia and 1629 patients with normokalemia. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for association between mild hyperkalemia and mortality during a median follow-up of 38-months. Results: All-cause mortality occurred in 36% and 38% of matched patients with normokalemia and mild hyperkalemia respectively (HR, 1.07; 95% CI, 0.90-1.26; P = 0.458). Unadjusted, multivariable-adjusted, and propensity-adjusted HRs for mortality associated with mild hyperkalemia were 1.33 (95% CI, 1.15-1.52; P < 0.0001), 1.16 (95% CI, 1.01-1.34; P = 0.040) and 1.13 (95% CI, 0.98-1.31; P = 0.091) respectively. Mild hyperkalemia had no association with cardiovascular or HF mortality or all-cause or cardiovascular hospitalization. Conclusion: Serum potassium 4-4.9-mEq/L is optimal and 5-5.5- mEq/L appears relatively safe in HF. Despite lack of an intrinsic association, the bivariate association of mild-hyperkalemia with mortality suggests that it may be useful as a biomarker of poor prognosis in HF. © 2008 Elsevier Ireland Ltd. All rights reserved.