The present study evaluated the safety and efficacy of patient-activated delivery of intrathecal morphine sulfate boluses delivered by way of a novel internalized intrathecal delivery system. Patients with refractory cancer pain or uncontrollable side effects were enrolled at 17 US and international sites in this prospective, open-label study. Pain relief, reduction in systemic opioid use, and reduction in opioid-related complications were analyzed both individually and together as a measure of overall success. One hundred forty-nine patients were enrolled and 119 were implanted. Average numeric analog scale pain decreased from 6.1 to 4.2 at 1 month and was maintained through month 7 (P <.01) and through month 13 (P <.05). Systemic opioid use was significantly decreased throughout the study (P <.01). Significant reduction in the opioid complication severity index was demonstrated at all 4 follow-up visits (P <.01). Overall success (>/=50% reduction in numeric analog scale pain, use of systemic opioids, or opioid complication severity index) was reported in 83%, 90%, 85%, and 91% of patients at months 1, 2, 3, and 4, respectively. This study demonstrated that patients with refractory cancer pain or intolerable side effects achieved better analgesia when managed with patient-activated intrathecal delivery of morphine sulfate via an implanted delivery system.