Background Among breast reconstruction methods, implant-based breast reconstruction has become the mainstream. However, periprosthetic infection is still an unresolved problem. Although published articles have revealed that limited use of antibiotics is sufficient to reduce infection rates, the number of surgeons still preferring elongated usage of antibiotics is not less. The aim of our study is to validate the appropriate duration of antibiotic use to reduce infection rate after implant-based breast reconstruction. Methods A retrospective study reviewed medical record of 235 patients (274 implants for reconstruction) who underwent prepectoral direct to implant breast reconstruction using acellular dermal matrix wrapping technique. Infection rates were analyzed for the patients administered postoperative prophylactic antibiotics until drain removal and those who received only perioperative prophylactic antibiotics for 24 hours. Results Of the 274 implants, 98 who were administered prophylactic antibiotics until drain removal had an infection rate of 3.06% (three implants) and 176 who received prophylactic antibiotics no longer than 24 hours postoperatively had an infection rate of 4.49% (eight implants). A total of 11 patients diagnosed with postoperative infection clinically, 8 were salvaged by antibiotic treatment, and 3 had implant removal and replacement with autologous flap. Postoperative antibiotic prophylaxis duration had no statistically significant effects in the risk of infection ( p = 0.549). Conclusion The duration of prophylactic antibiotics after surgery was not related to infection risk. Further study with a large number of patients, randomized control study, and route of antibiotics is needed.