Background and Aims: Severe pulmonary involvement in leptospirosis carries high mortality rates. It is the most common cause of death due to leptospirosis in many parts of India and the world. Exacerbated immune response of the host plays an important role in its pathogenesis. Hence, immunosuppressive drugs could be useful in its treatment. Glucocorticosteroids have been found to be useful in several studies. Cyclophosphamide, an immunosuppressive agent, has been found to be useful in a majority of pulmonary alveolar hemorrhages due to non leptospiral causes. This study was carried out to study the effects of cyclophosphamide in patients with leptospiral pulmonary alveolar hemorrhage. Method: A total of 65 patients with confirmed leptospirosis with severe pulmonary involvement admitted to a tertiary care center in south Gujarat were included in the study. All of the patients were treated with injection crystalline penicillin, methyl prednisolone pulse therapy, and non invasive mechanical ventilation. A total of 33 patients were given parenteral cyclophosphamide 60 mg/kg body weight stat on diagnosis. Their outcomes were compared with the remaining 32 patients who had not been given this drug. Survival was considered the main outcome indicator. Results: Out of the 33 patients treated with cyclophosphamide, 22 (66.7%) survived, while in the control group out of 32 patients, three (9.4%) survived. On statistical analysis, the odds ratio was 19.33 (4.22-102.13) and the P-value was < 0.001. Leucopenia (78.78%) and alopecia (18.75%) were the main side effects noted. No mortality was noted due to these side effects. Conclusion: Cyclophosphamide improves survival in cases of severe pulmonary alveolar hemorrhage due to leptospirosis. Statistically, the improvement is highly significant.