Background: Acute pancreatitis is a serious condition that requires prompt diagnosis and treatment. Serum amylase and serum lipase are two commonly used biomarkers for the diagnosis of acute pancreatitis, but there is ongoing debate about which marker is more accurate. Methods: We conducted a retrospective review of 70 patients diagnosed with acute pancreatitis at Dept of General Surgery, Mandya Institute of Medical Sciences, Mandya. We compared the diagnostic accuracy of serum amylase and serum lipase, and assessed the correlation between the two markers. Results: A total of 70patients were included in the study. The sensitivity and specificity of serum lipase were 81% and 98%, respectively, compared to 72% and 95% for serum amylase. The positive predictive value (PPV) of serum lipase was 98%, compared to 92% for serum amylase. The negative predictive value (NPV) of serum lipase was 54%, compared to 47% for serum amylase. There was a moderate positive correlation between serum amylase and serum lipase (r = 0.62, p < 0.001). Conclusion: Serum lipase is a more accurate diagnostic marker for acute pancreatitis than serum amylase, with higher sensitivity, specificity, PPV, and NPV. However, serum amylase can still be useful as an adjunctive diagnostic tool, particularly in cases where serum lipase levels are not available or inconclusive. The moderate positive correlation between the two markers suggests that they may be complementary in certain cases. Further studies are needed to determine the optimal cut off values for serum amylase and serum lipase, and to assess the diagnostic accuracy of these markers in different patient populations.