Background: Ventilator-associated pneumonia (VAP) is one of the most frequent hospital-acquired infections, which develops in mechanically ventilated patients after 48 hours of mechanical ventilation. The purpose of this study was to determine the incidence rate, various risk factors, microbiological profile, and outcome of early- vs late-onset ventilator-associated pneumonia (VAP) in medical intensive care unit (MICU). Materials and methods: This prospective study was conducted on 273 patients admitted to the MICU in JIPMER, Puducherry, from October 2018 to September 2019. Results: The incidence of VAP was 39.59 per 1000 ventilation days of MICU patients (93/273). Of these, 53 (56.9%) patients had early-onset VAP and 40 (43.1%) had late-onset VAP. Multiple logistic regression analysis showed that steroid therapy, supine head position, coma or impaired unconsciousness, tracheostomy, and re-intubation were found to be independent predictors of early- and late-onset VAP, respectively. Most cases of VAP were caused by Gram-negative bacteria (90.6%), with nonfermenters contributing to 61.8%. The most frequent pathogens causing early-onset VAP were Acinetobacter baumannii (28.9%) and Pseudomonas aeruginosa (20.6%), while in late-onset VAP, A. baumannii (32.9%) and Klebsiella pneumoniae (21.9%) were the most common. Maximum death rate was seen in patients infected with Escherichia coli (50%) and Stenotrophomonas maltophilia (38.5%). There was no significant association between the presence of VAP and mortality among the studied population. Conclusion: The incidence of VAP in our study was high. There were no significant differences in the prevalence of pathogens associated with early-onset or late-onset VAP. Our study shows that early-onset and late-onset VAP have different risk factors, highlighting the need for developing different preventive and therapeutic strategies.