Background: Clinical prediction rules have been designed to reduce variability and improve the diagnostic process. However, there are no unanimous criteria regarding which of them is the most efficient for the diagnosis of acute appendicitis. Aim: The primary aim of this study was to assess the diagnostic efficacy of the most commonly used clinical prediction rules. The second aim was to identify the combination of the smallest number of clinical and analytical variables that would allow a costeffective diagnostic approach. Methods: A retrospective observational study was conducted of 458 patients who were evaluated for right iliac fossa pain between January 2010 and December 2016. The scores tested were Alvarado, AIR, RIPASA, and AAS. Univariate and multiple regressions were used for validation. Results: Alvarado one was the most efficient to establish a positive diagnosis of acute appendicitis. However, the most simplified and predictive combination variables included anorexia, white blood cell count > 8275 leukocytes/μL, neutrophilia (> 75%), abdominal pain < 48 h, migrating pain, and temperature out the range of 37-39ºC. Conclusions: A new and effective CPR (HMC score) for predicting appendicitis in patients presenting with the right iliac fossa pain has been established.