Objective To estimate the effect of estrogen‐only and combined hormone replacement therapy (HRT) on the hazards of overall and age‐specific all‐cause mortality in healthy women aged 46–65 at first prescription. Design Matched cohort study. Setting Electronic primary care records from The Health Improvement Network (THIN) database, UK (1984−2017). Population 105 199 HRT users (cases) and 224 643 non‐users (controls) matched on age and general practice. Methods Weibull‐Double‐Cox regression models adjusted for age at first treatment, birth cohort, type 2 diabetes, hypertension and hypertension treatment, coronary heart disease, oophorectomy, hysterectomy, body mass index, smoking and deprivation status. Main outcome measures All‐cause mortality. Results A total of 21 751 women died over an average of 13.5 years follow‐up per participant, of whom 6329 were users and 15 422 non‐users. The adjusted hazard ratio (HR) of overall all‐cause mortality in combined HRT users was 0.91 (95% CI 0.88−0.94), and in estrogen‐only users was 0.99 (0.93−1.07), compared with non‐users. Age‐specific adjusted HRs for participants aged 46–50, 51–55, 56–60 and 61–65 years at first treatment were 0.98 (0.92−1.04), 0.87 (0.82−0.92), 0.88 (0.82−0.93) and 0.92 (0.85−0.98) for combined HRT users compared with non‐users, and 1.01 (0.84−1.21), 1.03 (0.89−1.18), 0.98 (0.86−1.12) and 0.93 (0.81−1.07) for estrogen‐only users, respectively. Conclusions Combined HRT was associated with a 9% lower risk of all‐cause mortality and estrogen‐only formulation was not associated with any significant changes. Tweetable Estrogen‐only HRT is not associated with all‐cause mortality and combined HRT reduces the risks. Tweetable Estrogen‐only HRT is not associated with all‐cause mortality and combined HRT reduces the risks.