Introduction: Acute appendicitis is a frequent cause of abdominal pain, affecting about 6-7% of people during their lifetime. Diagnosing it typically involves physical exam findings, lab tests, and imaging, but even with all these tools negative surgeries (i.e. removal of a non-inflamed appendix) still occur in up to ~20% of cases. Clinical scoring systems like the Alvarado score are used, but their reliability is variable. To improve diagnostic accuracy, new methods are being explored — one of them is using biomarkers related to platelet activation (such as mean platelet volume and platelet distribution width). The available evidence on these biomarkers is mixed, and my study aims to add more data on how accurate they are in diagnosing acute appendicitis. Objectives: To study the diagnostic accuracy of mean platelet volume in diagnosing acute appendicitis patients compared to histopathology as gold standard and to study the diagnostic accuracy of platelet distribution width in diagnosing acute appendicitis patients compared to histopathology as gold standard. Methodology: This was a diagnostic test evaluation study conducted among inpatients of the Department of General Surgery. A total of 43 patients were included. Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) were analysed from blood samples of patients undergoing emergency appendicectomy. Histopathology reports of the appendicectomy specimens were used as the reference standard, and the diagnostic accuracy, sensitivity, and specificity of MPV and PDW were assessed through statistical analysis. Results: Mean Platelet Volume (MPV) was evaluated in 53 patients. With a cutoff of 8.75, the ROC AUC was 0.768 (95% CI: 0.596-0.940; SE = 0.088; p = 0.002). At that cutoff MPV had a sensitivity of 83.33%, specificity 76.47%, positive predictive value 23.54%, negative predictive value 98.14%, positive likelihood ratio 3.54, negative likelihood ratio 0.21, and overall diagnostic accuracy of 81.13%. Platelet Distribution Width (PDW) had AUC of 0.787 (CI 0.609 – 0.965; SE 0.091; p < 0.001). With a cutoff of 12.35, PDW achieved sensitivity 92%, specificity 73.33%, PPV 23.09%, NPV 99.07%, positive likelihood ratio 3.45, negative likelihood ratio 0.10, but a lower diagnostic accuracy of 56.8%. Conclusion: From the current study it is concluded that platelet indices, Mean platelet volume and platelet distribution width might have a role in the diagnosis of acute appendicitis and might help to avoid possible negative appendicectomies.