The aim of this prospective cohort study was to evaluate the impact of tobacco smoke exposure, measured by maternal serum concentration of cotinine, on fetal midgestation biometric parameters and umbilical artery (UA) qualitative blood flow indices. The study population consisted of 114 healthy women in 20 to 24 weeks gestation who were recruited from the patients of two antenatal care units in Lodz, Poland. Significant negative correlation was found between fetal biparietal diameter (BPD) and serum cotinine concentration. Serum cotinine positively correlated with all blood flow indices under study (systolic/diastolic index [S/D], resistance index, and pulsatility index) after controlling for gestational age, gender, and femur length. The midgestation UA S/D ratio > 3 was found to be a significant risk factor for decreased birthweight. Tobacco smoke exposure is a significant factor inducing increased resistance of umbilical blood flow as measured in 20 to 24 weeks gestation. This could be one of the main mechanisms leading to decreased birthweight observed among infants with prenatal exposure to tobacco smoke.