Introduction: Acute appendicitis is traditionally a clinical diagnosis where there are a range of diagnostic accuracies reported. The role of ultrasound is to improve specificity and decrease negative appendicectomy rate. It is a simple, non-invasive, easily available technique. The purpose of this study is to determine the diagnostic accuracy of an ultrasound in combination with total leukocyte count, neutrophil percentage and C-reactive protein in diagnosing acute appendicitis. Methods: This study includes consecutive sampling of suspected patients from January 2021 to February 2022 with the approval of the ethical and research committee. Clinical and personal demographics and characteristics of patients were collected, including age, gender, symptoms and clinical signs. Ultrasonographic findings of fluid-filled appendiceal diameter of more than 6 mm, periappendiceal echogenic mesentry and an appendicolith were primary positive features. Laboratory inflammatory markers of total leukocyte count, neutrophil percentage and C-reactive protein were also included. Results: A total of 250 patients were included with a mean age of 25 ± 9.79 years. Total leukocyte count showed the highest sensitivity (77.68%), followed by neutrophil percentage (69.96%), C-reactive protein (67.10%) and ultrasound (62.96%). While ultrasound had the best specificity (70.59%), it was followed by C-reactive protein and total leukocyte count (64.71%) and neutrophil percentage (58.82%), respectively. The sensitivity and specificity (99% and 98%) increased significantly when all four tests were combined. Conclusions: Clinical assessment with laboratory inflammatory markers and ultrasound improves the early diagnosis of appendicitis and decreases the false-positive appendicitis diagnosis, hence saving surgeons’ time and relieving patients from unnecessary appendicectomies.