Background Effective postoperative analgesia is needed to prevent the negative effects of postoperative pain on patient outcomes. To compare the effectiveness of hydromorphone hydrochloride and sufentanil, combined with flurbiprofen axetil, for postoperative analgesia in pediatric patients. Methods This prospective randomized controlled trial included 222 pediatric patients scheduled for repair of a structural congenital malformation under general anesthesia. Patients were randomized into 3 groups: hydromorphone hydrochloride 0.1 mg/kg (H1), hydromorphone hydrochloride 0.2 mg/kg; (H2) or sufentanil 1.5 µg/kg (S). Analgesics were diluted in 0.9% saline to 100 ml and infused continuously at a basic flow rate of 2 mL per h. The primary outcome measure was the Face, Legs, Activity, Cry, and Consolability (FLACC) pain score. Secondary outcomes included heart rate (HR), respiration rate (RR), SpO2, Ramsay sedation scores, scores on the Paediatric Anaesthesia Emergence Delirium (PAED) scale, adverse reactions, parent satisfaction with analgesia. Results The FLACC score was significantly lower in H1 and H2 groups compared to S. The Ramsay sedation score was significantly higher in H1 and H2 groups compared to S. Recovery time was shorter in H1 group compared to patients H2 group or S group. There were no significant differences in the PAED scale, HR, RR, SpO2, adverse reactions, satisfaction of parents with analgesia, or length and cost of hospital stay. Conclusions Hydromorphone hydrochloride is a more effective analgesic than sufentanil for postoperative pain in pediatric patients following surgical repair of a structural congenital malformation, however, hydromorphone hydrochloride and sufentanil had similar safety profiles in this patient population. Trial registration Chinese Clinical Trial Register ChiCTR-INR-17013935). Clinical trial registry URL: Date of registration: December 14, 2017.