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Maternal smoking during pregnancy can induce structural and functional changes in the placenta. Placentas from heavy smoker (>20 cigarettes per day) mothers and non-smoker healthy controls (n=10 in each group) were enrolled in the present case-control study. Sample selection and sectioning were performed by systematic uniform random sampling (SURS). Selected sections were stained using Masson's trichrome to estimate quantitative parameters of placental extravillous trophoblast cells (EVTs) and the number of EVTs. Differences between groups were evaluated using the Mann-Whitney U-test, with significance set at P<0.05. There was a significant difference in placental weight and the total volume of the placenta between the heavy smoker and control groups (P<0.05). The total volume of EVTs, nucleus diameter, cytoplasm diameter, the volume of the nucleus and cytoplasm and the nucleus to cytoplasm ratio of EVTs were significantly greater in the heavy smoker compared with control group (P<0.05 for all). In placentas from heavy smokers, the total number of EVTs per unit volume of placental bed were significantly greater than in the control group (P<0.05 for both). In conclusion, the findings suggest that maternal smoking could affect fetal health by changing the quantitative parameters of the placenta, and likely the invasive properties of EVTs.