BACKGROUND: Postoperative pain is a frequent cause for delayed discharge following outpatient procedures, including anorectal surgery. Both central and peripheral pain receptor sensitization are thought to contribute to postoperative pain. Blocking these receptors and preempting sensitization prevents hyperalgesia leading to lower pain medication requirements. Studies in the orthopedic, urologic, and gynecologic literature support this practice, but the use of preemptive analgesia in anorectal surgery is understudied. OBJECTIVE: This study aimed to evaluate the effectiveness of preemptive analgesia in decreasing postoperative pain. DESIGN: This is a randomized, double-blinded, placebo-controlled trial. SETTING: This study was conducted at the University of Vermont Medical Center, a tertiary care referral center in Burlington, Vermont. PATIENTS: Patients who were over 18 years of age, ASA Physical Status Classes I, II, or III, and undergoing surgery for anal fissure, fistula or condyloma or hemorrhoids were selected. INTERVENTIONS: Preoperative oral acetaminophen and gabapentin followed by intravenous ketamine and dexamethasone were given before incision compared with oral placebos. MAIN OUTCOME MEASURES: The primary outcomes measured were postoperative pain scores, percentage of patients utilizing breakthrough narcotics, and rates of side effects. RESULTS: Ninety patients were enrolled. Because of patient withdrawal, screen failures, and loss to follow-up, 61 patients were analyzed (30 in the preemptive analgesia group and 31 in the control group). Patients in the active group had significantly less pain in the postanesthesia care unit and at 8 hours postoperatively. Significantly fewer participants in the active group used narcotics in the postanesthesia care unit and at 8 hours postoperatively. Average pain scores were excellent for both groups. There was no difference in the number of medication-related side effects between the 2 groups. LIMITATIONS: This study was limited by the small sample size and excellent pain control in both groups. CONCLUSIONS: Preemptive analgesia is safe and results in decreased pain in the early postoperative period following anorectal surgery. It should be implemented by surgeons performing these procedures. See Video Abstract at http://links.lww.com/DCR/A588.