We performed a case-control study to investigate the correlation between the apnea-hypopnea index (AHI) and the retinal vascular fractal dimension (FD). We selected 527 individuals who underwent polysomnography during health checkups at the Huadong Sanatorium from January to December 2021 as the study population, of whom 468 were included and 59 were excluded. All participants underwent a detailed health examination, including medical history assessment, physical examination, assessment of lifestyle factors, fundus photography, and laboratory examinations. The retinal vasculature was quantitatively assessed using Singapore I Vessel Assessment (SIVA) software. The relationship between the AHI and the retinal vessel quantitative was examined by multiple linear regression analyses and restricted cubic spline. Among the 468 studied individuals, the average age was 51.51 (43-58) years, with 369 (78.85%) men and 99 (21.15%) women. According to the AHI indicator, 355 individuals were diagnosed with obstructive sleep apnea (OSA) syndrome, with an average AHI of 17.00 (9.200-30.130) events/h; 113 individuals were classified as controls, with an average AHI of 2.13 (0.88-3.63) events/h. In multiple linear regression, following varying degrees of adjustment for confounding factors, FD was reduced by 0.013 (P = .012; 95% confidence interval [CI]: -0.024 to -0.003), FD arteriole (FDa) was reduced by 0.013 (P = .019; 95% CI: -0.024 to -0.002), and FD venule (FDv) was reduced by 0.014 (P = .08; 95% CI: -0.024 to -0.004) in the high-AHI group compared with the low-AHI group. All tests for trend P values were < .05. The restricted cubic spline in the overall OSA population and the individuals without diabetes revealed a U-shaped pattern of decreasing, then increasing, FD, FDa, and FDv with a rising AHI. In the OSA individual with diabetes, FD, FDa, and FDv gradually decreased with increasing AHI. The FD is associated with AHI in OSA individuals. The link between AHI and FD varied for OSA individuals with and without diabetes. Wang J, Chen T, Qi X, Li Y, Yang X, Meng X. Retinal vascular fractal dimension measurements in patients with obstructive sleep apnea syndrome: a retrospective case-control study. J Clin Sleep Med. 2023;19(3):479-490.