Objective: To investigate the association between a low unconjugated estriol (uE3) in the second trimester and adverse pregnancy outcomes. Methods: Three hundred nine women who underwent second-trimester maternal serum alpha-fetoprotein (AFP)-hCG-uE3 screening were divided into two groups: those with uE3 at most 0.75 multiples of the median (MoM) (n = 81) and those with uE3 exceeding 0.75 MoM (n = 228). Entry criteria included: hCG below 2 MoM, AFP below 2 MoM, age less than 35 years at delivery, complete prenatal records, and completed delivery. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for a variety of adverse pregnancy outcomes. Results: After adjusting for smoking and hCG, women with uE3 at or below 0.75 MoM were found to have significantly higher odds of developing fetal growth restriction, low amniotic fluid index (AFI), and small for gestational age (SGA) with ORs (and 95% CIs) of 6.73 (2.55,17.74), 3.85 (1.53, 9.68), and 2.89 (1.27, 6.57), respectively, for each of the outcomes. Conclusion: Low uE3 in the second trimester appears to be associated with fetal growth restriction, low AN, and SGA, and the risk seems to be independent of risk for adverse infant outcome associated with elevated AFP or hCG.