Resistant hypertension (RH) is a significant health problem with complex management. The aim of this study was to evaluate the risks and benefits of adding spironolactone to treat RH.In total, 216 patients with RH in whom spironolactone (12.5-25mg daily) was added as an antihypertensive were evaluated. One-hundred and twenty-five (125) were analysed retrospectively and 91 prospectively. Blood pressure (BP) and laboratory parameters (serum creatinine [sCrea], estimated glomerular filtration rate [eGFR] and serum potassium [sK]) were analysed at baseline and at 3-6-12 months after introducing spironolactone.A change of systolic/diastolic BP (mean±standard deviation) of -10.9±2.7/-4.3±1.6mmHg at 3 months and -13.6±2.8/-6.0±1.6mmHg at 12 months; p<0.001 was observed. These values were confirmed with ambulatory-BP monitoring at 12 months. At 3 months, an increase in sCrea of 0.10±0.04mg/dl, a decrease in eGFR of -5.4±1.9ml/min/1.73m and an increase in sK of 0.3±0.1mmol/l; p<0.001 was observed for all cases. These changes were maintained after 12 months. There were no significant differences in changes of BP, sCrea, eGFR and sK between 3 and 12 months. Results of the retrospective and prospective cohorts separately were superimposable. In the prospective cohort, spironolactone was withdrawn in 9 patients (9.9%) because of adverse effects.After 3 months with spironolactone, a decrease in BP associated with a decrease in the eGFR and an increase in sCrea and sK was observed. These changes were maintained at 12 months. Spironolactone is an effective and safe treatment for RH in patients with baseline eGFR ≥30ml/min/1.73m.