The objective of the study was to assess whether the association known in singleton pregnancies of high maternal serum α-fetoprotein (AFP) or human chorionic gonadotropin (HCG) with adverse outcomes applies also to multifetal gestations. Maternal serum AFP and HCG were evaluated in 207 multifetal pregnancies. High values were defined as a maternal serum AFP of > 4.5 and a HCG of > 4.0 multiples of the median (MoM), with appropriate adjustments. Results were correlated with premature delivery, stillbirths, or pregnancy termination for fetal anomalies. There were 10 stillbirths, 7 terminations of pregnancy for fetal anomalies, and 66 premature deliveries in the study group. Maternal serum AFP was somewhat higher in abnormal pregnancies than in those with normal outcome (3.4 vs. 2.5 MoM, respectively, NS). A high AFP level was found in 6% of pregnancies with adverse outcomes and in 4% of uncomplicated gestations (NS). High HCG values, also observed in 5% of cases, were all associated with normal outcome. Multiple marker screening suggested an increased risk for aneuploidy in 9% of patients, all of whom were euploid on amniocentesis karyotypes. Maternal serum screening in multiple gestations is confounded by the differing contributions of fetuses, and abnormal results cannot reliably predict adverse pregnancy outcomes