IMPORTANCE Optimal duration of antibiotic treatment to reduce infectious complications after an appendectomy for acute complicated appendicitis remains unclear. OBJECTIVE To investigate the effect of antibiotic duration on infectious complications after laparoscopic appendectomy for acute complicated appendicitis. DESIGN, SETTING, AND PARTICIPANTS National multicenter prospective, observational, surgical resident-led cohort study conducted in June and July 2014. This study involved academic teaching hospitals (n=8), community teaching hospitals (n=38), and community nonteaching hospitals (n=16), and all consecutive patients (n=1975) who underwent surgery for suspected acute appendicitis. EXPOSURES Patients treated laparoscopically for whom the antibiotic regimens were prolonged postoperatively because of complicated appendicitis. MAIN OUTCOMES AND MEASURES Receiving either 3 or 5 days of antibiotic treatment as planned and additional variables were explored as risk factors for infectious complications using regression analyses. RESULTS A total of 1975 patients were included in 62 participating Dutch hospitals; 1901 (96.3%) of these underwent an appendectomy for acute appendicitis and laparoscopy was used in 74.4% of these patients (n=1415). In 415 laparoscopically treated patients, antibiotic treatment was continued for more than 24 hours because of acute complicated appendicitis (29.3%). The prescribed antibiotic duration varied between 2 and 6 days in all of these patients. In 123 patients (29.6%), the length of treatment was adjusted. A shorter duration of antibiotic treatment (3 days instead of 5) had no significant effect on any infectious complication (odds ratio [OR], 0.93; 95% CI, 0.38-2.32; P=.88) or on intra-abdominal abscess development (OR, 0.89; 95% CI, 0.34-2.35; P=.81). Perforation of the appendix was the only independent risk factor for the development of an infectious complication (OR, 4.90; 95% CI, 1.41-17.06; P=.01) and intra-abdominal abscess (OR, 7.46; 95% CI, 1.65-33.66; P=.009) in multivariable regression analysis. CONCLUSIONS AND RELEVANCE Lengthening of postoperative antibiotic treatment to 5 days was not associated with a reduction in infectious complications. Further restriction of antibiotic treatment can be considered in nonperforated complicated appendicitis.