BACKGROUND: Platelets may act as vascular endothelial growth factor (VEGF) scavengers, possibly limiting neovascularization in retinopathy of prematurity (ROP). The purpose of this study was to investigate the association between thrombocytopenia (platelets <150,000/μL) and the development of type 1 ROP. METHODS: This was a retrospective 1:1 matched case-control study. Cases required laser; controls developed no or stage 1 ROP and were matched for birth weight within 100 g and gestational age within 1 week. Most recent platelet count prior to laser (case) and matched postmenstrual age (control) were abstracted. Conditional logistic regression was used. RESULTS: A total of 91 cases and 91 controls were reviewed. Of the cases, 25% had thrombocytopenia; of controls, 13% (P = 0.034; OR = 2.38; 95% CI, 1.04-5.43). Birth weight, gestational age, postmenstrual age, and culture-proven sepsis were not confounders in multivariate analysis. The association was significant for zone 1 (n = 16; OR = 9.00; 95% CI, 1.14-71.0) but not for zone 2 (OR = 1.43; 95% CI, 0.54-3.75) cases and controls. CONCLUSIONS: Thrombocytopenia was associated with type 1 ROP, primarily among infants with zone 1 ROP. This effect may result from disease location or disease timing, as posterior disease occurs at an earlier postmenstrual age. Longitudinal studies are required to further examine the roles of cumulative platelet deficits, thresholds, or critical time windows in the observed association.