Abstract Context Ventilator-associated pneumonia (VAP) is one of the most common causes of morbidity and mortality in mechanically ventilated patients. Curing and preventing effects of probiotics in promoting the growth of Bifidobacterium in the digestive system and the central role of bacteria colonization in the pathogenesis of VAP are evident. Aims The purpose of this study was to evaluate the effects of administration of commercially available probiotics, that is, orodispersible probiotic sachets on VAP prevention and clinical outcomes in critically ill patients. Settings and Design Randomized control trials. Methods and Materials In this study, 120 mechanically ventilated patients were randomly divided into two groups (n = 60 per group). Group 1 was given orodispersible probiotic sachets by gavage, twice a day in addition to routine care, while group 2 received only routine care. Demographic and clinical data were analyzed and clinical outcomes to the primary component (prevalence of VAP) and secondary component (other clinical factors) were interpreted. Statistical Analysis Used In this study, data were analyzed via SAS statistical software version 9.4, using Student's t-test, chi-squared test, repeated measure analysis of variance, and Wilcoxon test. Results There was a significant reduction in VAP diagnosed patients, as well as Clostridium difficile-associated diarrhea and some complications of mechanical ventilation, in group 1 in comparison to group 2. The improvement in VAP was significantly greater for group 1 as compared with group 2. However, the mortality rate was similar between two groups. Conclusions This study demonstrated that a daily diet with orodispersible probiotic sachets can be used as add-on therapy with other medications in the prevention of VAP. As a result, the use of orodispersible probiotic sachets in the treatment plan of patients undergoing long-term intubation is recommended.