Background: Unlike conventional immunotherapy, Cluster immunotherapy achieves maintenance dose in weeks along with omalizumab. However, safety of this method needs to be confirmed before wide spread application. Methods: We have designed open label observational study, to achieve maximum tolerance dose (MTD) in duration of six weeks with cluster Immunotherapy in immunologically significant sensitive patients to house dust mites in perennial rhinitis & Bronchial asthma. Results: With Combined omalizumab (anti-IgE) and cluster Immunotherapy, maintenance maximum tolerance dose (MTD) of 1000/ml achieved in 3 visits in 36 days (> 1month) in 9 patients without an IgE mediated adverse systemic reaction. Cluster Immunotherapy in 40 patients is efficacious, well tolerated than conventional immunotherapy of 4 months of single Allergen Injection as maintenance maximum tolerance dose (MTD) of 1000 - AU achieved in more than 75% in 4 visits of 46 days duration but 20% of patients in cluster Immunotherapy develop grade II/III adverse systemic reaction. Conclusion: Combined omalizumab (Anti - IgE) and cluster Immunotherapy is safe, effective and gives more rapid relief of symptoms.