To compare the postoperative analgesic effects of patient-controlled intravenous analgesia (PCIA) with hydromorphone or sufentanil on acute and chronic pain, anxiety, and depression in patients after cesarean section. Methods: A cohort of 339 eligible parturients scheduled for cesarean section were randomly divided into two groups. Following cesarean section surgery, one group of parturients was administered PCIA comprising sufentanil (sufentanil group), while the other was administered PCIA comprising hydromorphone (hydromorphone group). The post-operative pain score was measured by the numeric rating scale (NRS); patients were followed up by phone 3 months after surgery for assessment of chronic pain. Anxiety and depression were evaluated before surgery and 1 week after surgery by the Hospital Anxiety and Depression Scale (HADS). The Ramsay sedation scale was used to assess sedation 24 hours after surgery. Adverse reactions were documented. The 6-hour and 12-hour post-operative hemodynamics data and blood oxygen saturation of the two groups were recorded. Results: Compared to the sufentanil group, the hydromorphone group showed significantly lower pain scores during physical activity at 6 h and 12 h after surgery (P=0.001 and P=0.033, respectively) and a significantly lower pain score of uterine contraction within 48 h after surgery (P<0.05). The hydromorphone group showed a significantly lower HADS score (P<0.05) and incidence of chronic pain (P=0.047) after surgery compared to the sufentanil group. There was no significant difference in hemodynamics and Ramsay sedation score between the two groups (P>0.05). Conclusion: Hydromorphone PCIA can reduce acute and chronic pain, particularly internal organ pain, after cesarean section; it also can improve symptoms of anxiety and depression. These effects are greater than that of sufentanil. Hydromorphone can stabilize hemodynamics and yields few adverse reactions similarly to sufentanil.