Importance The administration of prophylactic antibiotics in obstetrics and gynecology represents a pivotal intervention with a major contribution to the prevention of maternal and neonatal infectious morbidity. Objective The aim of this study was to review and compare the most recently published guidelines on prophylactic antibiotic use in obstetric and gynecologic procedures. Evidence Acquisition A descriptive review of guidelines from the American College of Obstetricians and Gynecologists, the Society of Obstetricians and Gynaecologists of Canada, and the Royal Australian and New Zealand College of Obstetricians and Gynaecologists on antibiotic prophylaxis was carried out. Results There is a consensus among the reviewed guidelines regarding the importance of antibiotic prophylaxis prior to cesarean delivery, hysterectomy, colporrhaphy and surgical-induced abortions, the optimal choice of antibiotics, and the timing of administration, as well as the indications for increased and additional doses. First-generation cephalosporins are unanimously recommended as first-line antibiotics. All the reviewed guidelines recommend antibiotic prophylaxis in case of preterm prelabor rupture of membranes, whereas they discourage routine antibiotic use in case of active preterm labor with intact membranes or cervical cerclage placement. There is also an overall agreement that antibiotic prophylaxis should not be given for hysteroscopic and laparoscopic procedures with no entry into the bowel or the vagina, endometrial biopsy, intrauterine device insertion, or cervical tissue excision surgeries. Moreover, all the guidelines agree that women undergoing hysterosalpingography should receive a course of antibiotics only when the fallopian tubes are abnormal or there is a history of pelvic inflammatory disease. In contrast, inconsistency was identified on the need of antibiotic prophylaxis in case of obstetric anal sphincter injuries, operative vaginal delivery, and early pregnancy loss. Finally, American College of Obstetricians and Gynecologists states that antibiotics should not be routinely offered for oocyte retrieval and embryo transfer. Conclusions Infectious complications following both obstetric and gynecological procedures are significant contributors of morbidity and mortality, rendering their prevention using antibiotic prophylaxis a crucial aspect of preoperative care. Nevertheless, antibiotic overuse should be avoided. Thus, it seems of paramount importance to develop consistent international practice protocols for the appropriate use of antibiotics in everyday practice to minimize their adverse effects and maximize their associated benefits. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After participating in this activity, the learner should be better able to identify the obstetric and gynecologic procedures requiring antibiotic prophylaxis; discuss the indications of increased and repeat dosages of prophylactic antibiotics; and describe the optimal antibiotic regimens and the alternatives in case of allergic patients.