Introduction The most common surgical condition in children is appendicitis. However, making a diagnosis can be difficult due to poor communication and difficulty in the physical examination. Objective This study aimed to determine the accurate clinical predictive factors for the diagnosis of appendicitis in children in the emergency department (ED). Methods A retrospective cohort study was conducted from January 2015 to December 2019. The electronic medical records were reviewed from 1043 pediatric patients younger than 15 years with the chief complaint of abdominal pain and were admitted to the ED during the study period. The patients were divided into either the appendicitis group or non-appendicitis group. The two groups were compared in terms of baseline characteristics, abdominal symptoms and signs, symptom durations, laboratory results, final diagnosis, treatment in the ED, ED disposition, morbidity, and mortality. The significant predictive factors for the diagnosis of appendicitis were examined using univariate and multivariate analyses by logistic regression. Results Predictive factors for the diagnosis of appendicitis in pediatric patients with abdominal pain were gradual increase in abdominal pain (odds ratio (OR) 3.38, 95% confidence interval (CI) 1.51–7.58), right lower quadrant abdominal tenderness (OR 21.07, 95% CI 9.12–48.67), presentation of peritoneal irritation signs (OR 12.57, 95% CI 5.28–29.92), and an absolute neutrophil count >75% (OR 4.68, 95% CI 2.3–9.51). The significant variables were used to develop a diagnostic predictive probability scoring system that ranged from 0.05 to 0.95. The receiver operating characteristic curve indicated a cut-off point of 0.089 to predict pediatric appendicitis with an area under the curve of 0.963. Conclusion The predictive factors for diagnosing appendicitis in children are useful in determining which children require surgical intervention. However, the clinical symptoms and physical examination of the abdomen continue to be the most important diagnostic tools for the diagnosis of appendicitis in children.