OBJECTIVES: The purpose of this study was to determine the fraction of children with acute appendicitis who had recent false-negative diagnoses and to analyze the association of a missed diagnosis of appendicitis with patient outcome. METHODS: The records of all 816 patients who underwent appendectomy for suspected appendicitis at a free-standing children's hospital between 2007 and 2010 were reviewed. A patient admitted or evaluated in the emergency department (ED), discharged without a diagnosis of appendicitis, and then readmitted with histopathologically confirmed appendicitis within 3 days was considered to have a "missed diagnosis." Outcomes for this missed group were compared to those of the remainder of the appendectomy cohort. RESULTS: Thirty-nine patients with appendicitis (4.8%) were missed at initial presentation. The most common initial discharge diagnoses were acute gastroenteritis (43.6%), constipation (10.3%), and emesis (10.3%). The median duration from the initial evaluation to the appendicitis admission was 28.3 hours (interquartile range [IQR] = 17.0 to 39.6 hours). A missed diagnosis was associated with a longer median hospitalization (5.8 days [IQR = 4.0 to 8.1 days] vs. 2.5 days [IQR = 1.8 to 4.6 days]; p < 0.001), higher rate of perforation (74.4% vs. 29.0%; p < 0.001), higher complication rate (28.2% vs. 10.4%; p = 0.002), and higher rate of reintervention (20.5% vs. 6.2%; p = 0.003). CONCLUSIONS: Of children diagnosed with appendicitis, 4.8% may have had a missed opportunity for earlier diagnosis. These false-negative diagnoses are associated with higher rates of perforation, postoperative complications, and need for postoperative interventions, as well as longer hospitalizations.