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To evaluate the effect of a postpartum risk-based low-molecular-weight heparin protocol for venous thromboembolism prevention.We conducted a retrospective cohort study of postpartum women at a safety net hospital before (2013), during (2014), and after (2015) implementation of a risk-based enoxaparin thromboembolism prevention protocol. The calculated sample size was based on a primary outcome of enoxaparin administration rate. Secondary outcomes included incidence of postpartum thromboembolism, wound complications, and 30-day readmission rates. The prevalence of thromboembolism risk factors and protocol adherence was evaluated in two groups of women before (May 2013) and after (May 2015) protocol implementation. Exact χ2 or Cochran-Armitage trend tested differences in rates.Over 3 years, 9,766 deliveries were included. Enoxaparin was administered to 0.28% (95% CI 0.14–0.55) of postpartum women in 2013 (before) compared with 33.46% (95% CI 31.89–35.07%) after protocol implementation (P<.001). Although underpowered to detect a difference in these outcomes, no differences were seen in rates of thromboembolism (0.16%, 0.12%, 0.15%, P=.9), wound complication (0.82%, 1.21%, 0.91%, P=.7), or emergency department visits (8.30%, 7.96%, 8.34%, P=.9), whereas readmissions increased (0.79%, 1.27%, 1.42%, P=.02). Prevalence of thromboembolism risk factors did not differ between women delivered in May 2013 and May 2015. Physician adherence to the protocol was 89.5% in May 2015. Nine women had thromboembolic events after protocol implementation: five received appropriate treatment per protocol, but four did not. In 2014, three of four women with a thromboembolism were inadequately treated compared with one of five in 2015 with the addition of a computerized order set.Implementation of a low-molecular-weight heparin risk-based protocol for postpartum thromboembolism prevention resulted in high physician adherence and more than 30% of postpartum women receiving enoxaparin. Before implementing such a protocol on a wider scale, a much larger study is needed to evaluate the effect on thromboembolic disease and wound problems.