Background Acute appendicitis is a common surgical emergency, with diagnostic challenges that can lead to unnecessary surgeries. This study aims to compare the diagnostic accuracy of the Appendicitis Inflammatory Response (AIR) score and the Alvarado score in a clinical setting, examining the influence of demographic variables on their performance. Methods A retrospective analysis was conducted on 166 patients at National Guard Health Affairs Hospital, Saudi Arabia, from May 2016 to April 2022. Patients were categorized into two groups: 83 with appendicitis and 83 with acute abdominal symptoms but without appendicitis. We evaluated the diagnostic accuracy of the AIR and Alvarado scores through risk probability of developing appendicitis, sensitivity, and specificity. We also examined the effects of age and gender on the scores’ accuracy. Results The AIR score demonstrated higher overall sensitivity (95.7%) and specificity (90.5%) than the Alvarado score, which showed a sensitivity of 87.3% and a specificity of 52.4%. The AIR score was particularly effective in identifying patients with a high probability of appendicitis. Subgroup analysis revealed significant demographic influences, with men showing higher incidence rates of appendicitis and age impacting the scoring accuracy than women. Conclusions Our study’s findings advocate for the AIR score’s expanded use in clinical practice to improve diagnostic accuracy and patient management tailored to demographic variations. Further validation in varied clinical settings and larger cohorts is recommended.

Keywords: Keywords: Appendicitis, diagnosis, AIR score, Alvarado score