Background: Opioid guidelines recommend opioid rotation and switching for patients who do not achieve adequate pain relief or who experience intolerable adverse events (AEs) with their current opioid. However, specific recommendations and protocols for opioid rotation are lacking, making the practice time consuming and difficult for primary care physicians to accomplish independently or coordinate with a pain specialist. Objectives: To assess the safety and feasibility of using 24-hour intravenous patientcontrolled analgesia (IV-PCA) to achieve rapid opioid rotation and titration (RORT). Study design: Open-label pilot study. Setting: Hospital research center. Methods: At admission, patients (aged ≥ 18 years) with treatment-refractory chronic pain who were taking morphine or oxycodone for ≥ 3 months and had pain scores ≥ 4 on a 10- point scale, underwent opioid rotation to oral oxymorphone extended release (ER). They also received IV-PCA oxymorphone for 24 hours as needed. At discharge, the participants were taking oral oxymorphone ER with oxymorphone immediate release (IR) as needed based on their total 24-hour oral plus IV-PCA oxymorphone use. During a 2-week follow-up, their oxymorphone usage was titrated as needed. Main outcome measures were AEs, Patient Global Impression of Change (PGIC), Brief Pain Inventory (0 = no pain/interference, 10 = worst pain/ complete interference), treatment satisfaction, and change in oxymorphone dose. Results: Twelve patients enrolled and completed the 24-hour IV-PCA; 10 completed the 2- week follow-up post–24-hour IV-PCA. PGIC status improved by 12 hours (odds ratio [OR], 0.19, 95% CI, 0.08−0.44; P < 0.001), and both PGIC status and activity scores improved by 24 hours (OR, 0.23, 95% CI, 0.09−0.55; P = 0.001; OR, 0.49, 95% CI, 0.25−0.96; P = 0.04, respectively) and 2 weeks (OR, 0.14, 95% CI, 0.04−0.46; P = 0.001; OR, 0.21, 95% CI, 0.06−0.72; P = 0.01) versus 6 hours. During the 24-hour IV-PCA time period, 6 of 10 patients accomplished ≥ 50% of their overall dose titration. At 2 weeks, 8 of 10 participants were Greatly Satisfied or Somewhat Satisfied with the overall RORT procedure. RORT was well tolerated, with no serious AEs. Limitations: This was a pilot open-label study in a small number of participants. A larger randomized study with long-term follow-up and comparison to traditional protocols is necessary. Conclusions: Preliminary data suggest that RORT can be performed safely and effectively by incorporating IV-PCA during the first 24 hours. Further investigations are needed to determine whether RORT can become an ambulatory treatment intervention in pain practice. Clinicaltrials.gov registration: NCT00580294 Key words: chronic pain, opioid rotation, opioid switching, opioid substitution, opioid conversion, oxymorphone, oxycodone, morphine