Fentanyl is one of the most widely used opioids for intravenous patient-controlled analgesia (IV-PCA). Sufentanil, a fentanyl analog, is suitable for postoperative pain control because it has no active metabolites and shows a higher therapeutic index and lower frequency of respiratory suppression than fentanyl. This study aimed to compare the two opioids for postoperative pain relief on the basis of analgesic efficacy, adverse effects, and patient satisfaction. Sixty-four patients undergoing total laparoscopic hysterectomy were randomly allocated into a fentanyl group (n = 31) or a sufentanil group (n = 33). The patients received 50-μg fentanyl or 10-μg sufentanil before induction of anesthesia and 5 minutes after uterine incision during surgery in the fentanyl and sufentanil group, respectively. After arriving at the post-anesthesia care unit (PACU), verbal pain score (VPS) and sedation score were assessed. IV-PCA (fentanyl 1250 μg or sufentanil 250 μg with ondansetron 8 mg; total volume, 60 ml) was connected and continued for 48 h postoperatively. Postoperative pain was evaluated by using the numeric rating scale (NRS; at rest/during cough) at 6, 12, 24, 36, and 48 hours after surgery. The cumulative PCA consumption, patient satisfaction scores, and adverse effects were measured. In the PACU, VPS was significantly higher and rescue fentanyl consumption was higher in the fentanyl group than in the sufentanil group, while the sedation score and adverse effects were comparable between the groups. No significant differences were observed in the NRS scores for pain (at rest/during cough) in the ward over 48 hours postoperatively, but the cumulative PCA consumption was significantly higher in the fentanyl group (47.4 ± 9.9 ml vs. 36.2 ± 14.6 ml, = 0.01). There were no significant intergroup differences in patient satisfaction score and the incidence of adverse effects in the ward, except for a higher incidence of dry mouth in the fentanyl group. In comparison with fentanyl, sufentanil showed comparable analgesic efficacy and safety with less analgesic consumption (under a potency ratio of 1:5) in IV-PCA after total laparoscopic hysterectomy. Therefore, we suggest that sufentanil can be a useful alternative to fentanyl for IV-PCA.