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BACKGROUND Perioperative use of opioids has revealed significant adverse effects associated with poor postoperative outcomes. OBJECTIVE To determine whether opioid-free anaesthesia based on thoracic paravertebral block (TPVB) could improve postoperative recovery after breast cancer surgery. DESIGN A randomised controlled trial. SETTING A tertiary teaching hospital. PATIENTS Eighty adult women undergoing breast cancer surgery were enrolled. Key exclusion criteria included remote metastasis (but not to axillary lymph nodes of the surgical side), contraindication to interventions or drugs and a history of chronic pain or chronic opioid use. INTERVENTIONS Eligible patients were randomised at a 1 : 1 ratio to receive either TPVB-based opioid-free anaesthesia (OFA group) or opioid-based anaesthesia (control group). MAIN OUTCOME MEASURES The primary outcome was the global score of the 15-item Quality of Recovery (QoR-15) questionnaire at 24 h after surgery. Secondary outcomes included postoperative pain and health-related quality of life. RESULTS The QoR-15 global score was 140.3 ± 5.2 in the OFA group and 132.0 ± 12.0 in the control group (P < 0.001). The percentage of patients with good recovery (QoR-15 global score ≥118) was 100% (40/40) in the OFA group and 82.5% (33/40) in the control group (P = 0.012). Improved QoR in the OFA group was also evident in sensitivity analysis that rated QoR as excellent for a score of 136 to 150, as good at 122 to 135, as moderate at 90 to 121 and as poor at 0 to 89. The OFA group had higher scores in the domains of physical comfort (45.7 ± 3.0 versus 41.8 ± 5.7, P < 0.001) and physical independence (18.3 ± 2.2 versus 16.3 ± 4.5, P = 0.014). The two groups did not differ in pain outcomes or health-related quality of life. CONCLUSION TPVB-based opioid-free anaesthesia improved early postoperative quality of recovery without compromising pain control in patients undergoing breast cancer surgery. TRIAL REGISTRATION Clinicaltrials.gov; Identifier: NCT04390698.