AimsThis study aims to investigate the prognostic impact of mineralocorticoid receptor antagonists (MRAs) on cardiovascular events in patients hospitalized for acute decompensated heart failure with preserved ejection fraction (HFpEF; defined as left ventricular ejection fraction ≥45%).Methods and resultsA prospective multicentre cohort study was conducted in Nagano prefecture, Japan, between July 2014 and December 2018 that contained 518 consecutive HFpEF patients hospitalized for acute decompensated heart failure (HF). The primary outcome was a composite of cardiovascular death and HF readmission. We compared the incidence of cardiovascular events between patients who were prescribed with MRAs and those who were not in a propensity score matched cohort using a Cox proportional hazards regression model with a propensity score derived from 23 baseline variables. For sensitivity analysis, we conducted Cox proportional hazards regression models for the primary outcome adjusting for 16 clinically relevant variables in the crude cohort. The median age was 83 years, and 53% were female. The median left ventricular ejection fraction was 61%. During a median follow‐up of 553 days, the primary outcome occurred in 192 (37%) patients. MRAs were used in 255 (49%) patients. After analysis, a matched cohort consisting of 370 patients was created. After propensity score matching, the baseline characteristics were well balanced between the two groups. The incidence of the primary outcome was significantly lower in MRA users than in non‐users [32% (59/185) vs. 49% (90/185); hazard ratio (HR) 0.669, 95% confidence interval (CI) 0.482–0.929, P = 0.016]. The incidence of cardiovascular death was also significantly lower in the MRA users [11% (21/185) vs. 22% (41/185); HR, 0.563; 95% CI, 0.333–0.953; P = 0.032]. The risk of HF readmission tended to be lower in the MRA users [29% (54/185) vs. 41% (75/185); HR, 0.738; 95% CI, 0.520–1.048; P = 0.089]. MRA use was also associated with a lower risk of the primary outcome after Cox proportional hazards analysis adjusting for 16 clinically relevant variables in the crude cohort (HR, 0.710; 95% CI 0.507–0.995; P = 0.047).ConclusionsMineralocorticoid receptor antagonist use was significantly associated with a lower risk of the primary composite outcome of cardiovascular death and HF readmission in patients hospitalized for acute decompensated HFpEF. The incidence of cardiovascular mortality was also significantly lower in these patients.