Background Antibiotic de-escalation is an important strategy to conserve the effectiveness of broad-spectrum antibiotics. However, the outcome of this strategy for the treatment of ventilator-associated pneumonia (VAP) has not been widely studied in developing countries. Objectives To evaluate the outcome on intensive care unit (ICU) mortality, 28 days mortality, and length of ICU stay among VAP patients who receive de-escalation therapy. Setting This study was conducted in an ICU of a Malaysian public hospital. Method The electronic medical records of patients who developed VAP in the ICU were retrieved and relevant data was collected. Records of antibiotic prescriptions were also reviewed to collect the details of changes to antibiotic therapy (de-escalation). Main outcome measure Impact of antibiotic de-escalation on mortality. Results The mean age of the 108 patients was 46.2 ± 18.2 years; the majority being males (80%). The antibiotic de-escalation rate was about 30%. Out of this, 84% involved a change from broad to narrow-spectrum antibiotics and the remaining, withdrawal of one or more antibiotics. ICU mortality was 23% while 28 days mortality was 37%. There was no statistically significant difference in mortality rate, survival probability and the mean length of ICU stay between the de-escalation and the non-de-escalation group. However, patients with Simplified Acute Physiology Score II of ≥50 were significantly associated with ICU mortality and 28 days mortality. Conclusions In VAP patients, antibiotic de-escalation provides an opportunity to promote the judicious use of antibiotics without affecting the clinical outcomes.