Objective: To determine the diagnostic value of blood cells surface markers in patients with acute appendicitis. Methods: In this cross-sectional study, 71 patients who underwent appendectomy following a diagnosis of appendicitis were recruited during a one-year period. The patients were divided into two groups: patients with histopathologically confirmed acute appendicitis and subjects with normal appendix. Blood cell surface markers of all patients were measured. Univariate and multivariate analytical methods were applied to identify the most useful markers. Receiver operating characteristics (ROC) curves were also used to find the best cut-off point, sensitivity, and specificity.Results: Overall we included 71 patients with mean age of 22.6±10.7 years. Of the 71 cases, 45 (63.4%) had acute appendicitis while 26 (36.6%) were normal. There was no significant difference between two study groups regarding the age ( p=0.151) and sex ( p=0.142). The initial WBC count was significantly higher in those with acute appendicitis ( p=0.033). Maximum and minimum area under the ROC curve in univariate analysis was reported for CD3/RA (0.71) and CD38 (0.533), respectively. Multivariate regression models revealed the percentage of accurate diagnoses based on the combination of g/d TCR, CD3/RO, and CD3/RA markers to be 74.65%. Maximum area under the ROC curve (0.79) was also obtained for the same combination.Conclusion: the best blood cell surface markers in the prediction of acute appendicitis were HLA-DR+CD19, α/b TCR, and CD3/RA. The simultaneous use of g/d TCR, CD3/RA, and CD3/RO showed the highest diagnostic value in acute appendicitis.