Objective This post hoc, pooled, subgroup analysis of two randomised studies evaluated baseline characteristics that may influence the efficacy and safety of naldemedine in patients with opioid-induced constipation (OIC) and cancer.Methods Data for patients who received 0.2 mg naldemedine or placebo were pooled from randomised, placebo-controlled, phase IIb and phase III studies. Proportions of spontaneous bowel movement (SBM) responders and patients with diarrhoea were assessed for each treatment group. For the patient subgroups with or without possible blood–brain barrier (BBB) disruptions, changes in Numerical Rating Scale (NRS) and Clinical Opioid Withdrawal Scale (COWS) scores were assessed.Results A total of 307 patients were included in this analysis (naldemedine: n=155; placebo: n=152). The pooled proportion of SBM responders was 73.5% with naldemedine versus 35.5% with placebo. There was a significant increase in the proportion of SBM responders with naldemedine versus placebo (38.0% (95% CI 27.6% to 48.4%); p