Background: Clinical prediction rules have been designed to reduce diagnostic variability and improve the effectiveness of the diagnostic process. However, there are no unanimous criteria regarding which of them is the most efficient for the diagnosis of right iliac fossa pain. 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 cost-effective diagnostic approach to assess the right iliac fossa pain. 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 selected scores (Alvarado, AIR, RIPASA, and AAS) were applied to all cases to validate their effectiveness and simultaneously establish the smallest number of variables that were needed for an efficient diagnosis. Univariate and multiple regressions were used for validation. Results: Of the four scores tested, the Alvarado score was the most efficient diagnostic approach. However, the most reduced and predictive combination of the evaluated variables included anorexia, white blood cell count> 8275 leukocytes/μL, neutrophilia (>75%), abdominal pain < 48 hours, migrating pain to the right lower quadrant and axillary temperature out the range of 37-39ºC. Conclusions: A new and effective score for predicting appendicitis in patients presenting with right iliac fossa pain has been established.