Preeclampsia, intrauterine growth retardation (IUGR), oligohydramnios, abortus, preterm birth and premature rupture of the membranes (PROM) are significant complications of pregnancy. Insufficient trophoblastic invasion plays an important role in the pathophysiology of pregnancy complications. Soluble human leukocyte antigen-gestation (HLA-G)1/G5 is a molecule associated with trophoblast invasion. When pregnancy complications are predicted early, strategies to prevent these complications can be implemented. The aim of this study was to investigate the relationship between first trimester maternal serum soluble HLA-G1/G5 levels and high-risk pregnancies. A total of 232 pregnant women were followed prospectively. Maternal blood samples were collected for determination of soluble HLA-G1/G5 levels at 11-14 weeks, during which routine serum free beta human chorionic gonadotropin (βhCG) and pregnancy associated plasma protein-A (PAPP-A) level determinations in addition to nuchal translucency (NT) measurements for Down's syndrome screening were done during 20-22 weeks gestation. The subjects were classified into normal pregnancy, preeclampsia, oligohydramnios, IUGR, preterm birth and PROM groups. First trimester maternal serum soluble HLA-G1/G5 levels were not significantly different between the groups. First trimester soluble HLA-G1/G5 did not predict high-risk pregnancies. Studies with larger number of cases are need to confirm our findings.