Objectives/Hypothesis There are currently no established recommendations for the use of perioperative antibiotics (PAs) to prevent surgical site infections (SSIs) for direct microlaryngoscopy (DML). This study examined the incidence of SSI in patients undergoing DML with and without PAs. Study Design Retrospective, multi‐institutional chart review. Methods A retrospective, multi‐institutional chart review was performed at four tertiary referral academic medical centers. Patients undergoing DML from 2010 to 2017 were identified using Current Procedural Terminology codes. Medical records of patients undergoing DML with biopsy, microsurgery, laser ablation, or vocal fold injection who had adequate follow‐up were reviewed. Procedures with significant cartilage destruction, concurrent open surgery, or esophageal surgery were excluded. Data recorded included age, gender, pacemaker history, American Society of Anesthesiologists class, wound class, indication for surgery, use of laser, complications, emergency room visits, hospitalizations, pain, fever, and postoperative steroid and antibiotic prescriptions. Presence or absence of SSIs was evaluated by a fellowship‐trained laryngologist. Results There were 834 patients who met inclusion criteria. Of those, 698 did not receive PAs and 136 received PAs. The median age of patients was 54 years of age in the PA group and 57.5 years of age in the non‐PA group, and all cases were recorded as wound class II. Overall, 58% of surgeries involved use of carbon dioxide or potassium‐titanyl‐phosphate laser. Only one SSI was reported on follow‐up in a patient who did receive PAs. Conclusions SSIs are exceedingly rare following DML. PA use is not indicated for routine DML. Level of Evidence 4 Laryngoscope, 128:2838–2843, 2018