Background: Peripheral nerve blocks (PNBs) are increasingly popular in acute ankle fracture surgery but rebound pain may outweigh the benefits. The AnAnkle Trial was designed to assess the postoperative pain profile of PNB anaesthesia compared with spinal anaesthesia (SA). Methods: The AnAnkle Trial was a randomised, two-centre, blinded outcome analysis trial. Eligible adults booked for primary ankle fracture surgery were randomised to PNB or SA. The PNBs were ultrasound-guided popliteal sciatic and saphenous blocks with ropivacaine and SAs were with hyperbaric bupivacaine. Postoperatively, all subjects received paracetamol, ibuprofen, and patient-controlled i.v. morphine for pain. The primary endpoint was 27 h Pain Intensity and Opioid Consumption (PIOC) score. Secondary endpoints included longitudinal pain scores and morphine consumption separately, and questionnaires on quality of recovery. Results: This study enrolled 150 subjects, and the PNB success rate was >94%. PIOC was lower with PNB anaesthesia (median, –26.5% vs +54.3%; P<0.001) and the probability of a better PIOC score with PNB than with SA was 74.8% (95% confidence interval, 67.0–82.6). Pain scores and morphine consumption analysed separately also yielded a clear benefit with PNB, despite substantial rebound pain when PNBs subsided. Quality of recovery scores were similar between groups, but 99% having PNB vs 90% having SA would choose the same anaesthesia form again (P=0.03). Conclusions: PNB anaesthesia was efficient and provided a superior postoperative pain profile compared with SA for acute ankle fracture surgery, despite potentially intense rebound pain after PNB. Clinical trial registration: Clinicaltrialsregister.eu, EudraCT number: 2015-001108-76.