Objective: When evaluating suspected appendicitis, limited data support quality benchmarks for negative appendectomy (NA); none exist for delayed diagnosis of appendicitis (DDA). The objectives of this study are the following: (1) to provide preliminary evidence supporting a quality benchmark for DDA and 2) to compare presenting features and diagnostic evaluations of children with NA and DDA with those with pathologyconfirmed appendicitis (PCA) diagnosed during initial emergency department (ED) encounter.Methods: Secondary analysis of data from a QI project designed to reduce the use computed tomography when evaluating suspected appendicitis using a case-control design. Patients undergoing appendectomy in an academic tertiary care children's hospital system between January 1, 2015, and December 31, 2016 (n = 1,189) were eligible for inclusion in this case-control study. Negative appendectomy was defined as no pathologic change or findings consistent with a different diagnosis. Delayed diagnosis of appendicitis was defined as patients undergoing appendectomy within 7 days of a prior ED visit for a related complaint. Controls of PCA (n = 150) were randomly selected from all cases undergoing appendectomy.Results: There were 42 NA (3.5%) and 31 DDA (2.6%). Cases of PCA and NA exhibited similar histories, examination findings, and underwent comparable diagnostic evaluations. Cases of PCA more frequently demonstrated a white blood cell count greater than 10 Â 10 3 /μL (85% vs 67%; P = 0.01), a left-shift (77% vs 45%; P < 0.001), and an ultrasound interpretation with high probability for appendicitis (73% vs 54%; P = 0.03). Numerous significant differences in history, examination findings, and diagnostic tests performed existed between cases of PCA and DDA. Conclusions:Children with PCA and NA present similarly and undergo comparable evaluations resulting in appendectomy. A 3% to 4% NA rate may be unavoidable given these similarities. Presenting features in DDA significantly differ from those of PCA. An irreducible proportion of appendicitis diagnoses may be delayed.