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Background: We sought to improve the care of pediatric patients with possible appendicitis by decreasing unnecessary CT scanning. In an early QI initiative, we systematically emphasized the superiority of Ultrasonography (US) over CT, but did not find a decrease in CT utilization in practice. We therefore redoubled our initiative using a multimodal approach. We hypothesized a combined diagnostic and treatment pathway that allowed residual diagnostic uncertainty and used both surgery and antibiotic therapy for appendicitis that would decrease the need for diagnostic CT scanning. Results: Prior to implementation of the protocol, 33% of ER patients with appendicitis typical abdominal pain were treated for appendicitis (with surgery); after implementation, the total number treated remained unchanged 32.5% (p = NS), but the appendectomy rate dropped from 33 (204/619) to 23% after implementation of the pathway (96/ 419, p < 0.0005) with 50 patients treated with antibiotics. There was a reduction in CT scanning (pre 39% vs. 11%, p < 0.0001) while the use of US increased (pre 30% vs. 53%, p < 0.0001). The perforation rate decreased from 12 to 5% (p < 0.002) and negative appendectomy decreased from 13 to 4% (p < 0.0001). Of the 50 patients treated with antibiotics, 10 eventually crossed over to surgery. Conclusion: The use of a diagnostic and therapeutic pathway that offers antibiotic therapy for early probable appendicitis decreases the need for diagnostic CT scanning without increasing morbidity in pediatric appendicitis. Adherence to a medical/surgical treatment protocol that reserves surgery for clinically advanced appendicitis results in a reduction in CT scanning, perforation rates, negative appendectomy rates, and overall surgery for appendicitis.