Background: Autonomic dysfunction has a prognostic significance in various cardiovascular (CV) disorders, particularly atherosclerotic coronary artery disease (CAD). Previous studies are few, regarding the association of parasympathetic dysfunction with increased complications in patients with the acute coronary syndrome, a subset of CAD. We aimed to study the correlation of trends in the serum cholinesterase (sChE) levels, the marker of parasympathetic activity, with the occurrence of major adverse cardiovascular events (MACEs) in ST-segment elevation myocardial infarction (STEMI) patients. Methodology: We prospectively observed the levels of sChE in patients with STEMI on the day of admission, day 3, and day 5 along with routine biochemical profile, electrocardiogram, echocardiography, and coronary angiography. The patients were monitored during the hospital stay and were followed up at 1 month for the occurrence of any MACE. The MACE monitored was cardiac death, complete heart block, arrhythmias, and heart failure. The sChE levels are laboratory dependent and a value between 4000 and 14000 IU/L was considered normal in our laboratory. A value <4000 IU/L is noted as a low sChE level. The receiver operating characteristic curve was plotted for the cut off value of the sChE levels to predict the outcomes of patients. Results: Of the 100 STEMI patients studied, the sChE levels were persistently lower in patients who had MACE compared to those without MACE during the hospital stay and at month follow-up, which was statistically significant. A sChE <3745 IU/l on day 5 predicted an increased MACE with a sensitivity of 93.55% and specificity of 92.11%. Conclusion: A persistently low sChE levels from the day of admission can predict MACE in STEMI patients. Larger studies with prolonged follow-up are required for the causal association in the future.