Systemic opioids are immunosuppressive, which could promote tumour recurrence. We, therefore, test the hypothesis that supplementing general anaesthesia with neuraxial analgesia improves long-term oncological outcomes in patients having radical prostatectomy for adenocarcinoma. Patients who had general anaesthesia with neuraxial analgesia (n=1642) were matched 1:1 based on age, surgical year, pathological stage, Gleason scores, and presence of lymph node disease with those who had general anaesthesia only. Medical records were reviewed. Outcomes of interest were systemic cancer progression, recurrence, prostate cancer mortality, and all-cause mortality. Data were analysed using stratified proportional hazards regression, the Kaplan–Meier method, and log-rank tests. The median follow-up was 9 yr. After adjusting for comorbidities, positive surgical margins, and adjuvant hormonal and radiation therapies within 90 postoperative days, general anaesthesia only was associated with increased risk for systemic progression hazard ratio (HR)=2.81, 95% confidence interval (CI) 1.31–6.05; P=0.008 and higher overall mortality (HR=1.32, 95% CI 1.00–1.74; P=0.047). Although not statistically significant, similar findings were observed for the outcome of prostate cancer deaths (adjusted HR=2.2, 95% CI 0.88–5.60; P=0.091). This large retrospective analysis suggests a possible beneficial effect of regional anaesthetic techniques on oncological outcomes after prostate surgery for cancer; however, these findings need to be confirmed (or refuted) in randomized trials.