Background: For assisting in the early identification of acute appendicitis (AA) and its prompt therapy, several grading systems have been utilized. Because it takes into account the patient symptoms, findings, and laboratory assessment, the Alvarado score was chosen. Mean platelet volume (MPV) variations could be a sign of production of platelet in addition, a sign of changes in the severity of a number of disorders. Objective: This study aimed to compare MPV and Alvarado score to assess the predictive value for acute appendicitis. Patients and Methods: At the Emergency Hospital Mansoura University, Egypt, a prospective observational cohort research was conducted. 118 participants from both sexes who had right iliac fossa (RIF) pain suggestive of appendicitis participated in this study. Results: when compared to the histological findings, the Alvarado score exhibited a sensitivity and specificity of 67.6% and 61.5% respectively, with an accuracy of 58.5% in diagnosing appendicitis. With an accuracy of 79.7%, ultrasonography demonstrated a sensitivity and specificity of 80.4% and 76.9% in detecting appendicitis respectively. When compared to those without appendicitis, the MPV in cases with AA was statistically considerably smaller. The optimum MPV cutoff point for detecting appendicitis cases was less-than 8.92 with a sensitivity of 78.3%, specificity of 61.5%, and accuracy of 66.2%. Conclusion: While the Alvarado score and the combination of the two exhibited lower accuracy, the MPV had a greater accuracy for diagnosis than the Alvarado score. The sensitivity and accuracy of diagnosing acute appendicitis were significantly improved by combining the Alvarado score with the ultrasound examination.