Predictors of hyperkalemia in patients with cardiovascular disease (CVD; defined as patients with hypertension and heart failure) and associated chronic kidney disease (CKD) are not well established. The aim of this study was to ascertain risk factors of hyperkalemia (defined as serum potassium concentration >5.0 mEq/L) and associated all-cause mortality in patients with CVD treated with antihypertensive drugs that impair potassium homeostasis. In a retrospective analysis using a logistic regression model, risk factors for hyperkalemia and all-cause mortality were analyzed in 15,803 patients with CVD treated with antihypertensive drugs. The mean estimated glomerular filtration rate and mean serum potassium concentration were 55.55 ml/min/1.73 m² and 4.06 mEq/L, respectively. Hyperkalemia was observed in 24.5% of study patients and 1.7% of total hospital admissions. Compared to patients with normokalemia, those with hyperkalemia had a higher percentage of death (6.25% vs 2.92%, p = 0.0001) and admissions (7.80% vs 5.04%, p = 0.0001). Predictors of hyperkalemia were CKD stage (odds ratio [OR] 2.14, 95% confidence interval [CI] 2.02 to 2.28), diabetes mellitus (OR 1.59, 95% CI 1.47 to 1.72), coronary artery disease (OR 1.32, 95% CI 1.21 to 1.43), and peripheral vascular disease (OR 1.55, 95% CI 1.36 to 1.77). Predictors of all-cause mortality were CKD stage (OR 1.26, 95% CI 1.12 to 1.43), hyperkalemic event (OR 1.56, 95% CI 1.30 to 1.88), age (OR 1.04, 95% CI 1.03 to 1.05), and hospitalization (OR 1.04, 95% CI 1.04 to 1.05). In conclusion, hyperkalemia is encountered frequently in patients with established CVD who are taking antihypertensive drugs and is associated with increases in all-cause mortality and hospitalizations. Advanced CKD, diabetes mellitus, coronary artery disease, and peripheral vascular disease are independent predictors of hyperkalemia.