Objectives: To study the effect of maternal smoking on 2D ultrasound measurements and maternal serum (MS) levels of endocrinologic markers of placentation. Study design: Prospective population-based cohort study of 32 smokers and 96 non-smoking controls with a normal pregnancy outcome. Main outcome measures: Placental thickness and 2D-volume and MS levels of pregnancy-associated plasma protein A (PAPP-A) and free-beta human chorionic gonadotrophin (f beta hCG) at 11-13(+6) weeks of gestation and mid-trimester MS alpha-fetoprotein (AFP), unconjugated estriol (uE3) and inhibin A levels. Results: The MS levels of f beta hCG and PAPP-A were significantly (P < 0.01 and P < 0.001, respectively) lower in the serum and the level of inhibin A significantly (P <0.001) higher in the smokers than in controls. There was no significant difference for the MSAFP, MSuE3 placental thickness, basal plate surface and volume between the groups. Conclusion: The placental morphological alterations secondary to maternal smoking are mainly at the level of the villous trophoblast and are not associated with changes in the placental size or utero-placental interface during the first trimester of pregnancy. (C) 2013 Elsevier Ireland Ltd. All rights reserved.