Introduction: This study aimed to address the issue of antibiotic prescription processes in an Indian Intensive care unit (ICUs). Materials and methods:: In a prospective longitudinal study, all adult patients admitted in the ICU for 24 hours or above between 01 June 2020 and 31 July 2021 were screened for any new antibiotic prescription throughout their ICU stay. All new antibiotic prescriptions were assessed for baseline variables at prescription, any modifications during the course, and the outcome of antibiotic prescription. Results: A total of 1014 patients fulfilled entry criteria; 59.2 and 7.2% of days they were on a therapeutic or prophylactic antibiotic(s). Patients, who were prescribed therapeutic antibiotic(s), had worse ICU outcomes. A total of 49.5% of patients (502 of 1,014) received a total of 552 new antibiotic prescriptions during their ICU stay. About 92.13% of these prescriptions were empirical and blood or other specimens were sent for culture in 78.81 and 60.04% of instances. A total of 31.7% of episodes were microbiologically proven and were more likely to be prescribed by an ICU consultant. A total of 169 modifications were done in 142 prescription episodes; 73 of them after sensitivity results. Thus, the overall rate of de-escalation was 13.95%. Apart from the negative culture result (36.05%), an important reason for a relatively low rate of de-escalation was the absence of sampling (12.32%). Longer ICU stay before antibiotic prescription, underlying chronic liver disease (CLD), worse organ dysfunction, and septic shock were independently associated with unfavorable treatment outcomes. No such independent association was observed between antibiotic appropriateness and patient outcome. Conclusion: Future antibiotic stewardship strategies should address issues of high empirical prescription and poor microbiological sampling hindering the de-escalation process.