Introduction: Acute appendicitis represents a significant clinical challenge, necessitating accurate and prompt diagnosis to ensure effective treatment. This study aims to correlate clinical, biochemical, and radiological diagnoses with post-operative HPR findings of acute appendicitis patients. Materials/Patients and Methods: Prospective observational research was conducted on 168 patients who presented with features suggestive of acute appendicitis to the Department of General Surgery, B.L.D.E. (D.U.), VIJAYAPURA, KARNATAKA, from July 2022 to June 2024. Data were collected on patient demographics, clinical symptoms, physical examination findings, biochemical parameters (e.g., CRP, serum lactate), and radiological findings (Ultrasoundof abdomen and pelvis). Initial clinical, radiological, and biochemical findings were recorded and compared with post-operativehistopathological reports of the appendix. Results: The clinical diagnosis of acute appendicitis achieved a sensitivity of 100%, outperforming radiological diagnosis carried out using ultrasound(abdomen and pelvis), which had a sensitivity of 97.06% and CRP with levels ≥10.1 mg/l, which had a sensitivity of 89.71%. The sensitivity of lactate with levels ≥2.2 mmol/l was lower at 47.06%. Further, the results revealed that the clinical, radiological, and CRP levels are highly accurate and reliable, as the accuracy rate was84%, 80.95%, and 83.33%, respectively.However, the accuracy rate of lactate levels (46.43%) was limited. Conclusion: The study reaffirms the superior diagnostic accuracy of clinical diagnosis in managing acute appendicitis. While radiological and biomarker assessments provide valuable supplementary information. Elevated CRP and Lactate levels serve as important indicators of disease severity, guiding clinicians in risk stratification and management decisions.