Objective: In this prospective study, we investigated the association between mid-trimester maternal serum human chorionic gonadotropin (ms-hCG) levels and adverse pregnancy outcome in a South-Western Greek population. Materials and Methods: 130 healthy Greek women with spontaneous pregnancies were investigated for ms-hCG levels between the 13th and 24th weeks of gestation and followed for adverse pregnancy outcome. hCG levels > 2.0 multiples of the median value for gestation were considered abnormal. Statistical analysis was performed by Pearson’s chi-square test. Results: Gestational complications developed in a total of 12 of the 130 women studied (9.23%). Elevated ms-hCG levels were detected in a total of 14 of the 130 women studied (10.77%). Conclusion: Multiparameter testing of placental function in the mid-trimester (uterine artery Doppler, placental morphology and ms-hCG screening) may allow us to identify women with increased risk of developing severe placental insufficiency and pregnancy complications.