ABSTRACT: Postoperative pain after major open gynecologic surgeries requires appropriate pain management.This study aimed at comparing perioperative patient controlled epidural analgesia (PCEA) and patient controlled intravenous analgesia (PCA) after gynecologic oncology surgeries.In this clinical trial study, 90 patients with American society of anesthesiologists (ASA) class I or II scheduled for gynecologic oncologic surgeries were randomly allocated to two groups (45 patients each group) to receive: patient-controlled epidural analgesia with bupivacaine and fentanyl (PCEA group), or patient controlled intravenous analgesia (IV PCA group) with fentanyl, pethidine and ondansetron. Postoperative pain was assessed over 48 hours using the visual analog scale (VAS). The frequency of rescue analgesia was recorded. Occurrence of any concomitant events such as nausea, vomiting, ileus, purities, sedation and respiratory complications were recorded postoperatively.There were no statistically significant differences in demographic data including; age, weight, ASA physical status, duration of surgery, intraoperative bleeding, and the amount of blood transfusion (P > 0.05), between the two studied groups. Severity of postoperative pain was not significantly different between the two groups (P > 0.05); however, after first patient mobilization, pain was significantly lower in the epidural group than the IV group (P < 0.001). There was no significant difference between the two groups regarding the incidence of complications such as nausea, vomiting, purities or ileus (P > 0.05). Nevertheless, the incidence and severity of sedation was significantly higher in the IV group (P < 0.001). Respiratory depression was higher in the IV group than the epidural group; this difference, however, was not significant (P = 0.11). In the epidural group, only 10 patients (22.2%) had mild and transient lower extremities parenthesis.Both intravenous and epidural analgesic techniques with combination of analgesics provide proper postoperative pain control after major gynecologic cancer surgeries without any significant complications. Regarding lower sedative and respiratory depressant effects of epidural analgesia, it seems that this method is a safer technique for postoperative pain relief in these patients.