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Background: Optimal analgesic maintenance for severe cancer pain is unknown. This study evaluated the efficacy and safety of intravenous patient-controlled analgesia (IPCA) with continuous infusion plus rescue dose or bolus-only dose versus conventional oral extended-release morphine as a background dose with normal-release morphine as a rescue dose to maintain analgesia in patients with severe cancer pain after successful opioid titration. Methods: Patients with persistent severe cancer pain (≥7 at rest on the 11-point numeric rating scale [NRS]) were randomly assigned to 1 of 3 treatment arms: (A1) IPCA hydromorphone with bolus-only dose where dosage was 10% to 20% of the total equianalgesic over the previous 24 hours (TEOP24H) administered as needed, (A2) IPCA hydromorphone with continuous infusion where dose per hour was the TEOP24H divided by 24 and bolus dosage for breakthrough pain was 10% to 20% of the TEOP24H, and (B) oral extended-release morphine based on TEOP24H/2 × 75% (because of incomplete cross-tolerance) every 12 hours plus normal-release morphine based on TEOP24H × 10% to 20% for breakthrough pain. After randomization, patients underwent IPCA hydromorphone titration for 24 hours to achieve pain control before beginning their assigned treatment. The primary endpoint was NRS over days 1 to 3. Results: A total of 95 patients from 9 oncology study sites underwent randomization: 30 into arm A1, 32 into arm A2, and 33 into arm B. Arm B produced a significantly higher NRS over days 1 to 3 compared with arm A1 or A2 (PP=.024) among the 3 arms. No severe adverse event occurred in any arm. Conclusions: Compared with oral morphine maintenance, IPCA hydromorphone for analgesia maintenance improves control of severe cancer pain after successful titration. Furthermore, IPCA hydromorphone without continuous infusion may consume less opioid.