Women with antiphospholipid syndrome (APS) have an increased risk of adverse pregnancy outcomes. To define clinical, serologic, and treatment factors that can predict outcomes in pregnant women with APS. Retrospective cohort study of pregnant women with APS evaluated at a university medical center between January 2006 and August 2021. Demographics, personal and family history of thrombosis, autoimmune disease, antithrombotic use, pregnancy outcomes, maternal and fetal complications were collected. We compared pregnancy outcomes in the presence or absence of lupus anticoagulant (LA), systemic lupus erythematosus (SLE), prior thrombosis or pregnancy losses, and antithrombotic use. There were 169 pregnancies in 50 women; 79 (46.7%) occurred after maternal diagnosis of APS. The most common antithrombotic regimen was aspirin and low molecular weight heparin (LMWH) in 26.6% of pregnancies; 55.0% of all pregnancies and 68.4% of pregnancies post-APS diagnosis resulted in a live birth. In age-adjusted analyses, aspirin plus LMWH regardless of dosage was associated with significantly higher odds of live birth compared with no antithrombotic use (OR = 7.5, p < 0.001) and compared with aspirin alone (OR = 13.2, p = 0.026). SLE increased the risk for preterm birth and preeclampsia. A positive LA did not impact the outcomes evaluated and anticardiolipin IgM decreased the risk of pre-eclampsia. The presence of SLE is a significant risk factor for adverse outcomes in pregnant women with APS. Treatment with LMWH and aspirin was superior to aspirin alone. The creation of a global registry may be useful in improving the management of these patients.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.