Objective: To assess the prevalence of infectious complications and the protective effect of prophylactic antibiotic treatment after diagnostic office hysteroscopy in asymptomatic, infertile patients with normal results from transvaginal sonography. Design: Recording of infectious complications after routine hysteroscopy in the context of a randomized controlled trial; pseudorandomized, center-specific application of antibiotic prophylaxis. Setting: Two tertiary infertility care units. Patient(s): Six hundred thirty-one unselected, asymptomatic, infertile women who underwent routine, diagnostic hysteroscopy prior to a first in vitro fertilization (IVF) or intracytoplasmic sperm injection treatment. Intervention(s): Depending on the hospital and according to local protocols, hysteroscopy was performed with or without antibiotic prophylaxis. Main Outcome Measure(s): The prevalence of infectious complications after routine hysteroscopy. Result(s): Of the 631 women who underwent routine, diagnostic hysteroscopy, antibiotic prophylaxis was prescribed to 266 women, whereas 365 women underwent the procedure without prophylaxis. Only one infectious complication occurred (0.4%) in a patient who had not undergone therapeutic interventions and had taken antibiotic prophylaxis. This complication was successfully treated with antibiotics on an outpatient basis. Conclusion(s): Considering the extremely low risk of infectious complications and the lack of evidence, suggesting a beneficial effect of antibiotic prophylaxis, its use for routine, diagnostic office hysteroscopy should not be recommended. (Fertil Steril (R) 2011;95:792-4. (C)2011 by American Society for Reproductive Medicine.)