Introduction There is conflicting data regarding if patients with vascular extremity trauma who undergo surgical treatment need to be systematically anticoagulated. We hypothesized that intraoperative systemic anticoagulation (ISA) decreased the risk of repair thrombosis or limb amputation after traumatic vascular injury of the extremities. Methods We analyzed a composite risk of repair thrombosis and/or limb amputation (RTLA) between patients who did and did not undergo ISA during arterial injury repair. Patient data was collected in the American Association for the Surgery of Trauma PROspective Vascular Injury Treatment (PROOVIT) registry. This registry contains demographic, diagnostic, treatment, and outcome data. Results Between February 2013 and August 2015, 193 patients with upper or lower extremity arterial injuries who underwent open operative repair were entered into the PROOVIT registry. The majority were male (87%) with a mean age of 32.6 years (range 4–91) and 74% injured by penetrating mechanism. 63% of the injuries were described as arterial transection and 37% had concomitant venous injury. 62% of patients underwent ISA. RTLA occurred in 22 patients (11%) overall, with no significant difference in these outcomes between patients who received ISA and those that did not (10% vs. 14%, p = 0.6). There was, however, significantly higher total blood product use noted among patients treated with ISA versus those that did not receive ISA (median 3 units vs. 1 unit, p = 0.002). Patients treated with ISA also stayed longer in the ICU (median 3 days vs. 1 day, p = 0.001) and hospital (median 9.5 days vs. 6 days, p = 0.01). Discussion In this multicenter prospective cohort, intraoperative systemic anticoagulation was not associated with a difference in rate of repair thrombosis or limb loss; but was associated with an increase in blood product requirements and prolonged hospital stay. Our data suggest there is no significant difference in outcome to support use of ISA for repair of traumatic arterial injuries.