Pupillometry has proven effective for the monitoring of intraoperative analgesia in non-cardiac surgery. We performed a prospective randomized study to evaluate the impact of an analgesia-guided pupillometry algorithm on the consumption of sufentanyl during cardiac surgery. Fifty patients were included prior to surgery. General anesthesia was standardized with propofol and target-controlled infusions of sufentanyl. The standard group consisted of sufentanyl target infusion left to the discretion of the anesthesiologist. The intervention group consisted of sufentanyl target infusion based on the pupillary pain index. The primary outcome was the total intraoperative sufentanyl dose. The total dose of sufentanyl was lower in the intervention group than in the control group and (55.8 µg [39.7–95.2] vs 83.9 µg [64.1–107.0], p = 0.04). During the postoperative course, the cumulative doses of morphine (mg) were not significantly different between groups (23 mg [15–53] vs 24 mg [17–46]; p = 0.95). We found no significant differences in chronic pain at 3 months between the 2 groups (0 (0%) vs 2 (9.5%) p = 0.49). Overall, the algorithm based on the pupillometry pain index decreased the dose of sufentanyl infused during cardiac surgery.Clinical trial number: NCT03864016.