Epidural morphine as a single bolus dose has demonstrated analgesia that lasts up to 24 hours. Recent advances in drug delivery mechanisms have resulted in a formulation of morphine, DepoDur, which is a lipid-encapsulated extended-release epidural morphine that provides up to 48 hours of analgesia. The efficacy of DepoDur has been established after hip arthroplasty, lower abdominal surgery involving an incision below the umbilicus, and elective cesarean section delivery. The unique characteristics of DepoDur dictate that clinicians must be aware of the benefits and risks, and facilities must have a comprehensive system to allow for the safe administration of DepoDur. This article provides information on this novel drug delivery system, reviews research findings reported in the literature, and describes the relational collaboration system designed and implemented at Duke University Health System for safe patient care of DepoDur recipients.