Background: The most common cause of acute surgical abdomen is acute appendicitis and most commonly done emergency surgery is appendicectomy. Although a battery of tests and different scoring methods are available for diagnosis of acute appendicitis, it is very difficult to do prevent negative explorations for appendicectomy (15-30%). None of the tests has satisfactory sensitivity and specificity that can be relied upon. Objectives: The aim of the present study was to evaluate role of C-reactive protein (CRP), total leukocyte count, neutrophil count and ultrasonography (USG) of abdomen in diagnosing acute appendicitis and reducing the rates of negative appendicectomies. In addition, emphasis was given to whether combining the investigations in the same patient would improve the diagnostic accuracy. Materials and Methods: A total of 100 clinically diagnosed patients of acute appendicitis, posted for emergency appendicectomy were included in the study in General Surgery Department of Rajendra Institute of Medical Sciences, Ranchi during the period from September 2011 to October 2013. Preoperatively blood tests for CRP, total leukocyte count, differential leukocyte count (DLC) and USG abdomen were done. All patients were subjected to histological examination postoperatively, which was taken as the gold standard. The four investigations results were correlated with histo-pathological examination reports to evaluate their role in diagnosis of acute appendicitis. Results: In the present study, CRP has the highest sensitivity and specificity (90%, 80%) followed by USG (87.5%, 90%), white blood cells (WBC) count (78.75%, 80%) and neutrophil count (77.5%, 80%). Combining CRP and WBC count increases the sensitivity and specificity of the tests (96.25%, 80%). Conclusion: CRP contains important diagnostic information and hence should always be included in the diagnostic workup of acute appendicitis. The sensitivity of WBC count and DLC are low individually, but when combined with CRP the sensitivity and specificity increases. When all four tests are negative acute appendicitis is very unlikely and surgery can be safely deferred in these patients thereby reducing the negative appendicectomy rates.