Introduction: Perforated appendicitis very common abdominal emergency in children and nonoperative management with Ampicillin Gentamicin and Metronidazole (AGM) has shown good results. Recent data show that single daily dosing of Ceftriaxone and Metronidazole (CM) is as safe and effective as ampicillin gentamicin and clindamycin for treatment of perforated appendicitis after surgery in children. Treatment of complicated appendicitis in children with once daily CM can decrease the risk of in drug administration’s mistake, require the patient to be connected to the IV line for short time only once a day, may cause less IV line infection and may cost less. The aim of this study was to compare the effectiveness, and safety of CM with the traditional triple antibiotic for conservative treatment of complicated appendicitis children. Methods: A prospective, open, randomized study conducted from July 1st 2008 to June 30th 2009. Included were children younger than 14 years with complicated appendicitis who were randomly assigned to therapy with either CM as a single daily dose or AGM. The outcome variables compared were maximum daily temperature, duration of fever, time return to oral diet, length of antibiotic therapy, results of repeat WBC counts, need for abdominal abscess drainage, length of hospitalization and complication. Results: Overall 22 and 21 children were assigned to CM and AGM regimens respectively. There were no any significant differences in all clinical outcomes parameters between the two groups. Conclusions: Single daily dosing of CM is as safe and effective as the triple antibiotic regimen and has significant advantages for the conservative therapy of complicated appendicitis in children.