Background Most patients of empyema thoracis (ET) are frail, immunocompromised and have significant co-morbidities. Low levels of vitamin D appear to be a risk factor for tuberculosis as it modulates the T lymphocyte functions. The present study identifies the causal association and prognostic role of vitamin D levels in various stages of tubercular ET. Methodology Approximately 5 ml of fasting morning serum samples of patients with chronic tubercular and non-tubercular ET were obtained for 25(OH)D3 estimation. Both the groups were matched in terms of age, sex, nutritional status other comorbidities. The 25(OH)D3 levels were estimated using sandwich-ELISA technique. Statistical Analysis: The results were presented in frequencies, percentages and mean±SD. Unpaired t-test was used to compare the Vitamin D level between two strata. One-way analysis of variance (ANOVA) followed by Tukey’s post-hoc tests were used to compare the vitamin D level among the same strata. Results A total of 150 patients including 75 in tubercular and non-tubercular group were included. The vitamin D levels were significantly lower among tubercular as compared to non-tubercular patients (14.51±7.20 vs 28.30±11.54, 0.85 (0.79-0.91), p value .0001). Similarly, vitamin D levels were significantly low in stage III as compared to stage II and I (stage III 11.72±4.81, stage II 25.24±6.55, stage I 40.17±7.81 p value 0.0001). An overall better prognosis and outcome was observed in patients receiving vitamin D supplementation. Conclusion Serum levels of Vitamin D are associated with the severity of tubercular empyema. Vitamin D supplementation may be associated with better outcome and prognosis.