Background: The diagnosis of acute appendicitis clinically is challenging due to variant age groups at presentation; multidetector computed tomography (MDCT) has become the standard modality with high sensitivity and specificity. The American College of Radiology recommend the use of intravenous contrast-enhanced computed tomography for suspected cases but no explicit comment on the use of enteral contrast which create diversity in the literature for the appropriate MDCT protocols worldwide. The objective of this study is to compare the accuracy, sensitivity and specificity of variant MDCT protocols in diagnosing acute appendicitis. Methodology: A retrospective cross-sectional study was conducted at Alnoor Specialist Hospital – Makkah between January 2016 and December 2020 including all patients who presented to the emergency department with clinical suspicion of acute appendicitis and performed MDCT scans with subsequent surgical intervention. A net of 385 MDCT scans were retrieved from hospital System (PACS). Data processing was made on exported coded excel sheet data and analyzed by SPSS 26.0 statistical software. Results: 385 MDCT scans with different protocols were collected (NECT, ORAL only, IV only, ORAL and IV). Excluding ones without final diagnose 355 MDCT scans were analyzed. Radiologists’ability to detect acute appendicitis was higher in patients administered both oral and IV contrast (sensitivity =92.44%), IV only (89.61%), NECT (82.35%), and oral contrast (73.47%), respectively. Diagnostic accuracy was higher in patients administered both oral and IV contrast (accuracy = 89.23%). Conclusion: The present study demonstrates that the diagnostic accuracy and sensitivity in diagnosing acute appendicitis utilizing IV contrast are comparable to both IV and oral contrast; therefore, oral contrast administration can be omitted in routine appendicitis protocol. A higher specificity was found with the use of oral contrast due to the luminal filling of the appendix. Yet, it can be reserved for contraindicated cases to IV iodinated contrast administration. CT scan showed a hundred percent sensitivity in diagnosing perforated appendicitis regardless of the used protocol.