Background A survey to American Society for Surgery of the Hand members by Dunn et al showed that the use of preoperative antibiotics was random and not standardized for all hand procedures (Hand (N Y). 2020;15(4):534–541). Previous publications support that preoperative antibiotics for clean, soft-tissue procedures are not necessary, but there is minimal evidence regarding the need for preoperative antibiotics for hardware-based hand procedures. The purpose of our study is to compare infectious outcomes for patients undergoing hardware-based hand surgery between those who did and those who did not receive preoperative antibiotics. Methods A retrospective cohort analysis was performed on hardware-based surgical patients from the senior author's hand practice between January 2015 and October 2021. All patients either received imbedded permanent hardware or temporary percutaneous k-wire fixation. Exclusion criteria included polytrauma patients, patients with open hand wounds, and patients with less than 2 outpatient follow-up visits. Primary outcomes measured were 30- and 90-day postoperative antibiotic prescriptions and need to return to the operating room. Basic demographic information such as age, sex, body mass index, diabetes, and smoking status were recorded and compared. Results Four hundred seventy-two patients were reviewed, with 365 patients meeting inclusion and exclusion criteria. Two hundred twenty patients did not receive preoperative antibiotics and 145 patients did receive preoperative antibiotics. χ2 tests to analyze for associations between the variables were used. Thirteen patients in the no preoperative antibiotic group (5.9%), compared with 5 patients in the preoperative antibiotic group (3.4%), received a postoperative antibiotic prescription within 30 days (P = 0.288). Sixteen patients in the no preoperative antibiotic group (7.3%), compared with 8 patients in the preoperative antibiotic group (5.5%) received a postoperative antibiotic prescription within 90 days (P = 0.508). One patient in the nonantibiotic group required return to the operating room for irrigation and debridement. Conclusions There are no significant differences in the need for 30- and 90-day postoperative antibiotic prescriptions between those who did or did not receive preoperative antibiotics based on this single-surgeon experience.