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Although meperidine has been used for patient-controlled analgesia both intravenously (PCIA) and epidurally (PCEA), these routes have not been compared, and many studies have suggested that there is no advantage to the epidural route for administration of lipophilic opioids.A randomized, double-blind, crossover study was conducted for 24 h after cesarean section to compare the analgesic efficacy, side effects, patient satisfaction, drug use, and plasma drug concentrations with meperidine administered either as PCIA or as PCEA. Two groups, stratified for time of cesarean section during epidural anesthesia, postoperatively received either PCEA (group 1) or PCIA (group 2) with identical variables for 12 h before crossing to the other route for an additional 12 h.Results from 45 patients showed a similar speed of analgesic onset but, subsequently, significantly lower pain scores both at rest and with coughing in those receiving PCEA (P = 0.0001). Nausea and pruritus scores did not differ between the groups in the first 12 h postoperatively, but sedation scores were significantly higher with PCIA (P = 0.0001). Patient satisfaction scores and preference significantly favored PCEA (P - 0.0001), with almost 90% of participants preferring the epidural route. Meperidine use was reduced approximately 50% with PCEA (P = 0.0001), and plasma meperidine and normeperidine concentrations were significantly lower (P = 0.0001).We conclude that after cesarean section, PCEA with meperidine produces high-quality pain relief with few side effects and has significant advantages over PCIA meperidine. With the caveat that neonatal effects in breast-feeding mothers have yet to be evaluated, it can be highly recommended in this population.