BACKGROUND Adverse effects may still limit the use of continuous epidural and intravenous analgesia in surgical wards. This study postulated that postoperative epidural analgesia was more efficient, and had fewer side-effects than intravenous morphine. The aim was to investigate efficacy, adverse effects and safety of the treatments in a large patient population. METHODS During a five-year period 2696 patients undergoing major surgery, received either epidural or intravenous analgesia for postoperative pain relief. The patients were prospectively monitored in surgical wards. Pain was evaluated with a numeric rating scale (0-10) at rest/mobilization. Treatment duration, respiratory depression, sedation/hallucinations/nightmares/confusion, nausea/vomiting, pruritus, orthostatism/leg weakness, and insufficient pain relief were registered. Pain relief for all patients aimed at a pain scoring of less than 4 at rest. RESULTS Epidural analgesia was used in 1670 patients, and intravenous morphine in 1026 patients. Patients with epidural analgesia experienced less pain both at rest and during mobilization. Insufficient treatment effects such as dose adjustments, orthostatism/leg weakness, and pruritus were more common in the epidural group. Respiratory depression and sedation/hallucinations/nightmares/confusion occurred more often in the intravenous group. Thoracic epidural catheters caused a lower incidence of motor blockade compared to lumbar catheter placements. CONCLUSIONS In a large patient population the use of epidural and intravenous postoperative analgesia was considered safe in surgical wards, and the incidence of adverse effects was low. Patients with epidural analgesia experienced overall less pain, while opioid related side-effects were more common with intravenous morphine analgesia.