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The aim of this study was to identify risk factors for hyperkalaemia in a cohort of patients with newly diagnosed heart failure in the UK.A nested case–control study was conducted using data from The Health Improvement Network primary care database. A cohort of 19 194 patients aged 1–89 years between January 2000 and December 2005 with newly diagnosed heart failure was followed up and cases of hyperkalaemia identified. Cases were frequency matched to controls by age, sex, and calendar year, and information on demographics, co-morbidities, co-medications, and lifestyle factors was extracted from the database. Using unconditional logistic regression models, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to identify potential risk factors. In total, 2176 hyperkalaemia cases were identified over a mean follow-up of 3.9 years. Significant risk factors for hyperkalaemia were: renal failure (OR 3.81; 95% CI 3.29–4.42), type II diabetes (OR 1.52; 95% CI 1.31–1.75), valvular heart disease (OR 1.28; 95% CI 1.06–1.54), and current use of potassium-sparing diuretics (OR 3.01; 95% CI 2.61–3.48), ACE inhibitors (OR 1.70; 95% CI 1.41–2.04), trimethoprim (OR 2.82; 95% CI 1.88–4.23), non-steroidal anti-inflammatory drugs (OR 1.41; 95% CI 1.11–1.79), and several drug combinations. The risk was highest within the first month of medication use and decreased thereafter.Our findings may help to better identify patients with heart failure most likely to benefit from careful monitoring of serum potassium levels. Particular vigilance is needed during the start of treatment with certain medications.