Several randomized controlled trials comparing appendectomy to antibiotics alone in adults with acute appendicitis have been reported from non-U.S. countries. These studies reveal that non-operative management of appendicitis is a safe treatment for appendicitis and is associated with a significantly lower risk of complications than appendectomy. We have recently completed the first study in the U.S. examining the feasibility of non-operative management of uncomplicated appendicitis in children. In our pilot study, patients and their families chose between urgent appendectomy or antibiotics alone for treatment of uncomplicated appendicitis. The success rate of non-operative management was 90% at 30 days and 80% at a median follow-up of 8 months. In addition, patients in the non-operative group demonstrated a significantly faster return to normal activity and reported higher quality of life scores. The current proposal seeks to further investigate the effectiveness of non-operative management with antibiotics alone as a treatment option for children with uncomplicated appendicitis. When randomized trials are not feasible due to strong treatment preferences or when only a small proportion of patients will accept randomization, a parallel group non-randomized study where participants are allocated to their preferred treatment is a valuable alternative. Based on feedback from a multi-disciplinary stakeholder group that was convened to assess the potential impact of family preferences on study outcomes, recruitment, and generalizability, we propose a multi-institutional trial in which patients and their families choose between antibiotics alone (Non-operative group) or appendectomy (Surgery group). We hypothesize that non-operative management will be successful in 75% of patients at 1 year follow-up and will be associated with fewer disability days, higher quality of life scores, and lower costs than appendectomy. This study will enroll 795 patients, age 8-17 years, with uncomplicated appendicitis at 10 children's hospitals. The primary outcomes are: 1) differences in treatment-related disability between non-operative management and surgery in children with uncomplicated appendicitis across 10 children's hospitals; and 2) the success rate of non-operative management of uncomplicated appendicitis at 10 children's hospitals, defined as the percent of patients treated non-operatively who do not undergo an appendectomy. Secondary outcomes include differences between the groups in rates of complicated appendicitis, post-treatment related complications, disability days of the parent, quality of life and healthcare satisfaction measures, and total costs and the incremental cost-effectiveness of non-operative management relative to appendectomy. The proposed study will expand upon our previous pilot study by including patients from both freestanding and non-freestanding children's hospitals with both urban and rural demographies to determine the success rate and morbidity associated with non-operative management in a population that better represents the overall population of children in the U.S. Successful completion of this study may provide evidence for the effectiveness of non-operative management of uncomplicated appendicitis as an alternative first line therapy in children.