Background Azithromycin is an azalide antibiotic with an extensive range of indications and has become a common treatment option due to its convenient dosing regimen and therapeutic advantages. Human studies addressing gestational use of azithromycin have primarily focused on antibiotic efficacy rather than fetal safety. Our primary objective was to evaluate the possibility of teratogenic risk following gestational exposure to azithromycin. Methods There were 3 groups of pregnant women enrolled in our study: 1) women who took azithromycin. 2) women exposed to non-teratogenic antibiotics for similar indications, and 3) women exposed to non-teratogenic agents. They were matched for gestational age at time of call, maternal age, cigarette and alcohol consumption. Rates of major malformations and other endpoints of interest were compared among the three groups. Results Pregnancy outcome of 123 women in each group was ascertained. There were no statistically significant differences among the three groups in the rates of major malformations; 3.4% (exposed) versus 2.3% (disease matched) and 3.4% (non teratogen) or any other endpoints that were examined. In the azithromycin group, 88 (71.6%) women took the drug during the first trimester Conclusion Results suggest that gestational exposure to azithromycin is not associated with an increase in the rate of major malformations above the baseline of 1–3%. Our data adds to previous research showing that macrolide antibiotics, as a group, are generally safe in pregnancy and provides an evidence-based option for health professionals caring for populations with chlamydia.