Background: Allergic fungal rhinosinusitis (AFRS) is a distinct form of chronic rhinosinusitis. Type I hypersensitivity to inhaled fungal allergens has been implicated as key pathogenesis. Immunotherapy as one of the therapeutic options is still controversial. Objective: to evaluate the role of immunotherapy in the management of AFRS patients not responding to medical treatment 3 months following endoscopic surgery. Methodology: A total of 35 patients diagnosed as resistant AFRS were included in this prospective study. Patients were diagnosed following clinical, radiological, and endoscopic examination of nose and paranasal sinuses. Specimens were collected during endoscopy and subjected to microscopic examination and fungal culture. Skin prick test and assessment of total IgE level were performed for all patients. Sublingual immunotherapy (SLIT) was initiated for all patients for 6 months. Clinical efficacy of SLIT was assessed using the 20-item sino-nasal outcome test (SNOT-20) score. Results: Aspergillus spp. was the most frequent fungus isolated (74.3%) from patients. All patients were sensitized to mixed fungi. Elevated total IgE (> 100 IU/mL) was found in all patients with 40% of them had peripheral eosinophilia. A significant improvement (p < 0.001) was recorded in the SNOT-20 score of examined patients recording a mean of 1.2 ± 0.3, 6 months after SLIT compared to 1.93 ± 0.44 before immunotherapy initiation. Conclusion: Immunotherapy appears to be a good adjunctive therapy for the management of resistant cases of AFRS.