ABSTRACTImportanceNeonatal appendicitis (NA) is a rare and potentially fatal neonatal disease. However, misdiagnosis is common owing to atypical clinical manifestations and non‐specific laboratory tests.ObjectiveThe aim of this study was to summarize the clinical characteristics, treatments, and prognoses of infants with NA.MethodsThis retrospective analysis included 69 patients diagnosed with NA admitted to Beijing Children's Hospital between 1980 and 2019. The patients were divided into surgical and non‐surgical groups based on whether surgery was performed. Their clinical characteristics were analyzed using the chi‐square test, t‐test, or the Mann‐Whitney U test.ResultsThe study included 47 males and 22 females with NA. The primary symptoms were abdominal distension (n = 36, 52.2%), fever (n = 19, 27.5%), refusal to feed or decreased feeding (n = 16, 23.2%), and vomiting (n = 15, 21.7%). Sixty‐five patients underwent abdominal ultrasound examinations; 43 had definite appendiceal abnormalities, 10 had right lower abdominal adhesive masses, and 14 had neonatal enterocolitis manifestations. Twenty‐nine and 40 patients were in the surgical and non‐surgical groups, respectively. No statistically significant differences were observed between the groups regarding sex, age at onset, birth weight, admission weight, or hospitalization time. However, parenteral nutrition was prolonged in the surgical group (P = 0.001). Additionally, two patients (2.9%) died.InterpretationNA is a rare neonatal disease with atypical clinical manifestations. Abdominal ultrasonography may aid in the diagnosis. Similarly, appropriate treatment can improve the prognosis.