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Introduction and objectives Potassium derangements are frequent among patients with chronic cardiovascular conditions. Studies on the associations between potassium derangements and clinical outcomes have yielded mixed findings, and the implications for health care expenditure are unknown. We assessed the population-based associations between hyperkalemia, hypokalemia and clinical outcomes and health care costs, in patients with chronic heart failure, chronic kidney disease, diabetes mellitus, hypertension, and ischemic heart disease. Methods Population-based, longitudinal study including up to 36 269 patients from a health care area with at least one of the above-mentioned conditions. We used administrative, hospital and primary care databases. Participants were followed up between 2015 and 2017, were aged ≥ 55 years and had at least 1 potassium measurement. Four analytic designs were used to evaluate prevalent and incident cases and the use of renin-angiotensin-aldosterone system inhibitors. Results Hyperkalemia was twice as frequent as hypokalemia. On multivariable-adjusted analyses, hyperkalemia was robustly and significantly associated with an increased risk of all-cause death (HR from Cox regression models ranging from 1.31–1.68) and with an increased odds of a yearly health care expenditure > 85th percentile (OR, 1.21–1.29). Associations were even stronger in hypokalemic patients (HR for all-cause death, 1.92–2.60; OR for health care expenditure > percentile 85th, 1.81–1.85). Conclusions Experimental studies are needed to confirm whether the prevention of potassium derangements reduces mortality and health care expenditure in these chronic conditions. Until then, our findings provide observational evidence on the potential importance of maintaining normal potassium levels.