Objective. To investigate which serologic and clinical findings predict adverse pregnancy outcome in patients with antiphospholipid antibody (aPL) and to test the hypothesis that a pattern of clinical and serologic variables can identify women at highest risk of adverse pregnancy outcome. Methods. Women enrolled in a multicenter prospective observational study of risk factors for adverse pregnancy outcome in patients with aPL (lupus anticoagulant [LAC], anticardiolipin antibody [aCL], and/or antibody to β2- glycoprotein I [anti-β2GPI]) and/or systemic lupus erythematosus (SLE) were recruited for the present prospective study. Demographic, clinical, serologic, and treatment data were recorded at the time of the first study visit. The relationship between individual and combined variables and adverse pregnancy outcome was assessed by bivariate and multivariate analysis. Results. Between 2003 and 2011 we enrolled 144 pregnant patients, of whom 28 had adverse pregnancy outcome. Thirty-nine percent of the patients with LAC had adverse pregnancy outcome, compared to 3% of those who did not have LAC (P < 0.0001). Among women with IgG aCL at a level of ≥40 units/ml, only 8% of those who were LAC negative had adverse pregnancy outcome, compared to 43% of those who were LAC positive (P = 0.002). IgM aCL, IgG anti-β2GPI, and IgM anti-β2GPI did not predict adverse pregnancy outcome. In bivariate analysis, adverse pregnancy outcome occurred in 52% of patients with and 13% of patients without prior thrombosis (P = 0.00005), and in 23% with SLE versus 17% without SLE (not significant); SLE was a predictor in multivariate analysis. Prior pregnancy loss did not predict adverse pregnancy outcome. Simultaneous positivity for aCL, anti-β2GPI, and LAC did not predict adverse pregnancy outcome better than did positivity for LAC alone. Conclusion. LAC is the primary predictor of adverse pregnancy outcome after 12 weeks' gestation in aPL-associated pregnancies. Anticardiolipin antibody and anti-β2GPI, if LAC is not also present, do not predict adverse pregnancy outcome.