Background: Mechanical ventilation is a lifesaving intervention for critically ill pediatric patients but is also associated with high morbidity and mortality. Identifying modifiable risk factors is essential to improve outcomes. Aim: To identify risk factors associated with mortality among mechanically ventilated children admitted to a tertiary care Pediatric Intensive Care Unit. Methods: This prospective observational study was conducted on 300 children aged 1 month to 12 years who underwent mechanical ventilation in the PICU over 11 months. Data on demographics, clinical parameters, and complications were collected. Statistical analysis included t-tests, chi-square tests, and logistic regression, with a significance threshold of p < 0.05. Results: The mortality rate among ventilated children was 38.0%. Demographic and general clinical parameters such as age, sex, PRISM score, duration of hospital and PICU stay did not show significant association with mortality. However, certain complications, including ventilator-associated pneumonia (15.3%, p = 0.028), nosocomial sepsis (19.7%, p = 0.004), and urinary tract infection (14.3%, p = 0.023) were significantly associated with increased mortality risk. Conclusion: Nosocomial infections, especially VAP and sepsis, are key predictors of mortality in ventilated children. Focused infection control practices and early management of complications are crucial to reducing mortality in this vulnerable population.