Introduction: The WHO launched a 5-year global initiative to address the problem of medication errors on March 29, 2017, targeting a decrease in severe and avoidable medication-related harm by 50% in all the countries. Since prescription errors are preventable, this study was conducted to determine incidence and severity of medication prescription errors (MPEs). Settings and design: Intensive care unit of a tertiary care academic hospital, prospective observational study. Methods and materials: For all patients admitted in a medical ICU, baseline data (demographic, APACHE II, length of ICU stay, and days of mechanical ventilation) were noted. Treatment charts were reviewed daily, and each prescription was compared against a master chart prepared using standardized references to study the incidence of prescription errors. Severity classification was done using National Coordinating Council for Medication Error Reporting and Prevention (NCCMERP) classification. Mean and median, along with standard deviation and interquartile range, were calculated for all quantitative variables. Multivariate linear regression analysis model was used. Results: Out of the total 24,572 medication orders, 2,624 had prescription errors, an error rate of 10.7% (95% CI, 10.3–11.1). When analyzed for severity, 1,757 (7.15%) (95% CI, 6.8–7.5) MPEs did not result in patient harm and 867 (3.52%) (95% CI, 3.3–3.8) MPEs required interventions and/or resulted in patient harm. Patients with deranged creatinine (p <0.001) and INR (p = 0.024) had higher number of severe MPEs. Conclusion: The incidence of MPEs in the medical ICU at the tertiary care hospital was 10.7%, 3.52% being severe errors.