This is a randomised, controlled, unmasked clinical trial evaluating whether topical antibiotic prophylaxis reduces the rate of infection after oculofacial plastic surgery compared to a non-antibiotic ointment. A total of 401 participants over the age of 18 were recruited, with 13 either lost to follow-up or did not receive surgery. Those within the antibiotic group received 0.5% Erythromycin ophthalmic ointment, Bacitracin zinc 500 unit/gram ophthalmic ointment, or Bacitracin zinc plus Polymyxin B sulfate 500 unit-10,000 unit/gram ophthalmic ointment. The placebo arm received ophthalmic lubricant ointments comprising mineral oil and petrolatum. All participants were instructed to apply their assigned ointment to the surgical site four times daily for seven days post-surgery. The first postoperative assessment occurred seven to 14 days post-surgery. However, participants were able to seek care earlier if an adverse event occurred. Surgical site infection was identified in 2.7% of participants from the placebo arm, and 0% of those in the antibiotic arm. This study demonstrates that topical antibiotic ointment following oculofacial plastic surgery reduces surgical site infection compared to an application of nonantibiotic ointment. As the primary outcome was fortunately low, a limitation of this study is that this hindered further secondary subgroup analyses. Indeed, further multi-institutional collaboration would be useful in identifying patients or surgery characteristics that would most benefit from topical antibiotic prophylaxis.