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In regard with the effect of immune-stimulants in the treatment of infectious diseases, the effect of vitamin D administration on the outcome of patients with Ventilator-Associated Pneumonia (VAP) with a high rate of mortality, was studied.In this trial, 46 adult patients suffering from VAP and vitamin D deficiency were enrolled. The first group of patients received single intramuscular injection of vitamin D (300000 Unit), while the other group were given the placebo.Administration of vitamin D significantly enhanced its levels (P < 0.0001) in the treated patients (12.28 ± 8.26) in comparison with placebo group (1.15 ± 1.50). Serum Interleukin-6 levels were significantly reduced in the treated group compared to placebo (P = 0.01). Although C-Reactive protein (CRP) levels showed an improving trend in the vitamin D group, no significant difference between groups (P = 0.12) was found. Interestingly, the mortality rate of patients that treated with vitamin D (5/24) was significantly lower (p = 0.04) than that of the placebo group (11/22).Our results indicate that vitamin D administration can significantly reduce the IL-6 as prognostic marker in VAP patients, and must be considered as adjunct option in the treatment of VAP patients.vitamin D deficiency was very common in the studied VAP patient population (97%).vitamin D can diminish the levels of IL-6 in the serum of VAP patients, and that these finding were associated with a lower mortality rate.vitamin D supplementation can be considered as a suitable therapeutic intervention in VAP patients.