Background <p>This study compared the effectiveness of cabergoline and hydroxychloroquine in preventing ovarian hyperstimulation syndrome (OHSS) in patients with polycystic ovary syndrome (PCOS) undergoing controlled ovarian stimulation.</p> Materials and methods <p>This double-blind, parallel, and randomized clinical trial was performed from April to June 2024. Forty-two patients with PCOS who were candidates for assisted reproductive techniques were randomized into two groups. The first group received 0.5&#xa0;mg of cabergoline, and the second group received 400&#xa0;mg of hydroxychloroquine for 8 days. Then, ultrasounds were conducted on days 3 and 5 after oocyte retrieval to assess for OHSS.</p> Results <p>Three and five days after oocyte retrieval, laboratory findings, and clinical outcomes were similar between the cabergoline and hydroxychloroquine groups. Key laboratory parameters, including hemoglobin, hematocrit, sodium, potassium, blood urea nitrogen, and creatinine, did not show significant differences between the groups. On day three, OHSS incidence didn’t have a significant difference between the hydroxychloroquine and cabergoline groups, both for the mild (31.58% vs. 42.86%) and moderate (15.79% vs. 9.52%) groups. Mild cases were observed in one of the patients in both groups 5 days after pickup (<i>p</i> = 0.942). No patients in the cabergoline group required hospitalization or treatment, compared to one in the hydroxychloroquine group (<i>p</i> = 0.127).</p> Conclusion <p>The incidence of OHSS was similar between cabergoline and hydroxychloroquine, with no significant differences observed in laboratory parameters or clinical outcomes after oocyte retrieval. However, given the study’s sample size, further research is needed before these findings can be generalized to a larger population.</p> Clinical trial number <p><a href="http://www.irct.ir">http://www.irct.ir</a>; Registration number: IRCT20240305061171N1; Registration date: 2024 June 29.</p>