Introduction Tolvaptan is indicated for the treatment of patients with autosomal dominant polycystic kidney disease (ADPKD) at risk of rapid progression. Subjects aged 56–65 years were enrolled in the pivotal REPRISE trial but constituted only a small proportion of the population. We performed a pooled analysis to evaluate the effects of tolvaptan on decline in estimated glomerular filtration rate (eGFR) in subjects aged >55 years. Methods This was a pooled analysis of data on subjects aged >55 years with ADPKD from 11 studies of tolvaptan or non-tolvaptan standard of care (SOC). Data on individuals who participated in >1 study were linked longitudinally to provide maximum duration of follow-up. Tolvaptan and SOC subjects were matched for age, sex, eGFR, and chronic kidney disease (CKD) stage to minimize confounding. Treatment effects were compared using mixed models with fixed effects for treatment, time, treatment-by-time interaction, and baseline eGFR. Results In the pooled studies, 230 tolvaptan-treated and 907 SOC subjects were aged >55 years at baseline. Ninety-five subjects from each treatment group could be paired according to the matching criteria, all in CKD G3 or G4 and ranging in age from 56.0–65.0 years (tolvaptan) or 55.1-67.0 years (SOC). The eGFR annual decline rate was significantly reduced by 1.66 ml/min/1.73 m2 (95% confidence interval, 0.43 to 2.90; P=0.009) in the tolvaptan group compared to SOC over 3 years. Conclusion In subjects aged 56-65 years with evidence of rapid progression, tolvaptan exhibited efficacy similar to that seen in the overall indication.