This prospective, randomized, controlled investigation compared the effects of three prophylactic mu-opioid antagonists, epidural butorphanol (BU) 3 mg, epidural nalbuphine (NB) 10 mg, and oral naltrexone (NX) 6 mg, on postcesarean epidural morphine analgesia. After randomization, 102 term parturients underwent cesarean delivery with epidural anesthesia, 2% lidocaine and epinephrine 1:200,000. When the umbilical cord was clamped, each patient received one epidural solution (containing morphine 4 mg plus either saline or treatment drug), and one oral capsule (containing either placebo or treatment drug) in a double-blind manner. Maternal outcomes included pain and satisfaction [assessed with 100-mm visual analog scales (VAS)], and the incidence and severity of respiratory depression, somnolence, pruritus, nausea, and emesis. Through the first 12 h postpartum, the BU group achieved significantly greater analgesia than the morphine sulfate (control) (MS), NB, and NX groups, a significantly lower incidence of severe pruritus than the MS group, and significantly greater satisfaction than MS and NX groups. Epidural morphine and BU promoted better analgesia and satisfaction than any previously documented postcesarean regimen.