Background/Objectives: Preoperative antithrombotic therapy is common among patients undergoing subdural hematoma (SDH) evacuation. However, the association with postoperative outcomes remains uncertain. We evaluated this potential association using a multicenter electronic health record cohort and a single-center cohort. Methods: We performed a retrospective cohort study using TriNetX, a multicenter electronic health record (EHR) database, and a single-center cohort. TriNetX was used to identify adults undergoing evacuation of nontraumatic subdural hematoma between 2005 and 2025. The exposed cohort was defined as documented oral anticoagulant or antiplatelet exposure within 7 days before surgery, after which patients were propensity-score matched 1:1. The single-center cohort included surgically treated subdural hematoma patients with clinical, radiographic, laboratory, and operative data. Postoperative outcomes included 30-day mortality, short-term thrombotic complications, and 90-day repeat subdural hematoma surgery. Results: In TriNetX, 15,651 eligible patients were identified. Matched cohorts included 1455 exposed and 1455 unexposed patients. Preoperative antithrombotic exposure was associated with higher 90-day repeat surgery (9.7% vs. 6.5%; hazard ratio [HR] 1.52; p = 0.001), whereas 30-day mortality and 14-day thrombotic complications did not differ significantly. The single-center cohort included 164 surgically treated patients, including 103 exposed and 61 unexposed patients. The reoperation association was not reproduced. However, exposed patients had higher unadjusted 30-day and overall mortality that attenuated after multivariable Cox adjustment. Conclusions: Preoperative antithrombotic exposure was associated with repeat surgery in the TriNetX cohort but not in the single-center cohort. Together, these findings suggest that antithrombotic exposure may identify a medically complex surgical SDH population requiring individualized postoperative surveillance.