Background: Acute appendicitis remains the most common cause of acute abdominal pain necessitating operative intervention. Although postoperative antibiotics are universally used for perforated appendicitis, no consensus exists on whether postoperative antibiotics are beneficial for preventing surgical site infections (SSIs) in nonperforated cases. We set out to determine how postoperative antibiotic therapy affects outcomes after appendectomy for nonperforated appendicitis. Study Design: The medical records of 1,000 patients undergoing appendectomy for nonperforated appendicitis at The Mount Sinai Medical Center from January 2005 through July 2010 were retrospectively reviewed. Results: In total, 728 cases contained sufficient follow-up data for analysis; 334 of these patients received postoperative antibiotics and 394 did not. There were no significant differences in patient demographics, medical comorbidities, American Society of Anesthesiologists (ASA) class, admission temperature, preoperative antibiotic treatment, operating room time, estimated blood loss, appendiceal diameter, or intraoperative transfusion between the two groups, although WBC was higher for patients receiving postoperative antibiotics (12.3 vs 14 cells/mm 3, p = 0.001). Postoperative antibiotics did not alter the incidence of superficial SSIs, deep SSIs, or organ space SSIs (all p = 0.1), but did correlate with higher rates of Clostridium difficile infection (p = 0.02), urinary tract infection (p = 0.05), postoperative diarrhea (p < 0.001), and longer length of stay (LOS) (1.1 vs 2.4 days, p < 0.001). Patients receiving postoperative antibiotics also showed trends toward higher readmission and reoperation rates (both p = 0.06). Conclusions: Postoperative antibiotic treatment for nonperforated appendicitis did not reduce infectious complications and prolonged LOS while increasing postoperative morbidity. Therefore, postoperative antibiotics likely increase the treatment cost for nonperforated appendicitis while not adding an appreciable clinical benefit and, in some cases, actually worsening outcomes.