BACKGROUND AND OBJECTIVE: Data regarding hemorrhagic complications of direct oral anticoagulants (DOACs) and vitreoretinal surgery are limited. PATIENTS AND METHODS: Multicenter analysis of longitudinal, aggregated electronic health records of patients undergoing pars plana vitrectomy (PPV) with no prior history of ocular hemorrhage. Retrospective analysis of patients undergoing PPV between January 1, 2013, and December 31, 2019. The main outcomes were development of postoperative hemorrhagic complications within 1 month following vitreoretinal surgery. RESULTS: A total of 58,131 eyes underwent PPV, with 2,956 (5.1%) on anticoagulant medication prior to surgery. Eight hundred twenty-eight eyes (1.4%) developed a postoperative hemorrhage. Of eyes with anticoagulation use, 50 of 2,956 (1.29%) developed a hemorrhage, whereas 778 of 55,175 (1.41%) of the eyes with no prior anticoagulation use developed a postoperative hemorrhage (P = .2107). CONCLUSION: Use of DOACs prior to vitreoretinal surgery does not appear to be associated with increased rates of postoperative intraocular hemorrhage.