A fetus identified to be at risk for chromosomal abnormalities may benefit from identification of genetic defects through amniocentesis. Although the risks associated with amniocentesis are considered to be minimal, being an invasive procedure it is not completely without complications. Background and Objectives: The current study aims to identify correlations between blood contamination of samples collected during amniocentesis and certain factors dependent on the instruments used (thickness of the needle used to aspirate the fluid), the location of the placenta, and uterine vascularity (more pronounced in multiparous patients). Materials and Methods: The study included 190 patients in the second trimester of pregnancy who met one of the criteria for invasive prenatal diagnosis (age over 35 years, high risk in first trimester screening, history of pregnancies with genetic abnormalities, etc.). The amniotic fluid samples collected from these patients were analyzed in terms of blood contamination of the amniotic fluid aspirated with maternal cells Results: Of the patients in whom the procedure was performed using 21 G size needles, 16 samples (13.33% of the total) were contaminated. None of the samples collected from patients where a 20 G needle was used were contaminated. There was a statistically significant association between the lack of contamination and the use of Doppler ultrasound in multiparous patients with anterior placenta in whom a 21-gauge needle was used for amniocentesis. Conclusions: There is an increased rate of sample contamination (statistically significant) when using 21 G needle sizes and a significant difference in contamination between primiparous and multiparous patients, with contamination being more frequent in multiparous patients. The use of Doppler ultrasonography may benefit the procedure, as the contamination rate was significantly reduced when used during amniocentesis.