Aims: To determine whether antenatal administration of low-molecular-weight-heparin (LMWH) reduces the recurrence of adverse pregnancy outcomes (APO). Study Design: Retrospective cohort study. Place and Duration of the Study: Inova Alexandria Hospital, Alexandria, VA and Georgetown University Medical Center, Washington, DC during the period of January 1, 2006 and December 31, 2009. Methodology: All pregnant women with history of APOs, including preeclampsia or abruption at <35 weeks, birth weight <5th centile, fetal loss at ≥20 weeks, or ≥2 spontaneous losses between 12 and 20 weeks, were administered LMWH or not at the discretion of the managing physician. Excluded were cases with antiphospholipid Original Research Article Kamda et al.; IBRR, Article no. IBRR.2014.005 141 syndrome. The independent effect of LMWH on recurrence was assessed using logistic regression analysis with odds ratios (OR) having 95% confidence interval (CI) not inclusive of the unity considered significant. Results: Of the 140 women in the cohort, 44 (31%) received LMWH during the subsequent pregnancy and the remainder did not. APO recurred in 23.6% (33/140). Logistic regression analysis demonstrated that LMWH significantly and independently lowered the risk of recurrent APO (adjusted OR=0.08, 95% CI 0.01-0.45), whereas history of fetal growth restriction (OR=3.88, 95% CI 1.51-9.99) and positive results for inherited thrombophilias (OR=6.96, 95% CI 1.58-30.67) increased the risk. Conclusion: In patients with rigorously defined history of severe APO, prophylaxis with LMWH is associated with a significant reduction in recurrence of severe APO.