Introduction: Venous thromboembolism (VTE) is a leading cause of mortality in the postpartum period. Several autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus and Crohn’s disease, have been found to increase risk of VTE by upregulating the body’s procoagulants while decreasing physiologic anticoagulants via systemic inflammation. No existing studies have estimated the association of these risk factors exclusively among postpartum women. Hypothesis: Presence of autoimmune disease will be associated with increased risk of VTE among postpartum women. Methods: We identified a cohort of 755,722 women ages 15-45 with an international classification of disease code (ICD) for delivery in the 2011-2017 U.S. MarketScan Commercial administrative database. The exposure of prevalent autoimmune disease, represented by 29 endocrine, antibody positive, digestive and vascular diseases, was identified by two or more inpatient or outpatient ICD codes occurring before a woman’s delivery date. VTE events between the delivery hospital discharge and 12 weeks postpartum were defined using validated algorithms of ICD codes and confirmatory evidence of anticoagulant prescriptions. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) adjusted for age, hypertension, gestational diabetes, preeclampsia, multiple gestation and antepartum hemorrhage. Associations were also evaluated separately by specific autoimmune disease category (endocrine, antibody positive, digestive, vascular). Results: The average age of women was 30.7 years (SD: 5.4 years) and 27,322 out of the 755,722 deliveries (3.6%) occurred among women with prevalent autoimmune disease. Of these, 10,555 were endocrine diseases (1.4%), 12,851 were antibody positive diseases (1.7%), 4,634 were digestive diseases (0.6%) and 353 were vascular diseases (0.1%). There were 3,502 postpartum VTE events; among them 235 (6.7%) occurred in women with prevalent autoimmune disease. In the adjusted model, women with autoimmune disease had higher postpartum rate of VTE (HR: 1.54; 95%CI: 1.25, 1.90) relative to those without. When evaluating the subgroups separately, the rate of VTE was elevated among women with digestive (HR: 1.73; 95%CI: 1.09, 2.76) and antibody positive (HR: 1.82; 95%CI: 1.38, 2.39) autoimmune diseases. Conclusions: Women with autoimmune disease were at 50% greater risk of postpartum VTE as compared to women without these conditions. The association was more pronounced for women with digestive and antibody positive autoimmune disease. Given the importance of maternal mortality as an outcome, these findings suggest value for increasing VTE awareness among women with these autoimmune conditions and their healthcare providers.