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Introduction: Ventilator Associated Pneumonia (VAP), continues to complicate a significant proportion of critically ill mechanically ventilated patients, resulting in increased morbidity, mortality and hospital costs. Probiotics offer a novel approach to the prevention of VAP. Uncertainty still exists regarding its benefit for the prevention of VAP. Aim: To study the efficacy of probiotic prophylaxis in preventing VAP in the Medical Intensive Care Unit (MICU) of a tertiary hospital in Southern India. Materials and Methods: The study was a prospective, randomised, double-blind, placebo controlled trial that included 146 critically ill, mechanically ventilated adult patients admitted to a 24 bed MICU. Patients in the probiotic group received 2×109 Colony Forming Units (CFU) of Lactobacillus rhamnosus on a twice daily basis (as oral slurry and via nasogastric tube) upto seven days, while those in the placebo arm received identical appearing inert base powder. The primary outcome was incidence of VAP as defined by the clinical criteria of Johansen. Secondary outcomes included duration of mechanical ventilation, MICU stay, hospital stay and mortality. The differences in means and proportions between the two study groups were assessed using independent-t-test and twosample proportion tests respectively. Results: The incidence of VAP, though lower in the Lactobacillus arm, was not statistically significant- (10% vs. 11%, Lactobacillus vs. placebo). Other outcomes including ICU mortality, median time to VAP, duration of mechanical ventilation, duration of ICU and hospital stay were also not significantly different in the two groups. There were no episodes of Lactobacillus bacteraemia. Conclusion: In critically ill, adult patients admitted to the MICU administration of Lactobacillus rhamnosus did not prevent VAP. ICU mortality, in hospital mortality and median time to VAP were also not influenced by the administration of probiotics.