To assess the clinical efficacy and safety of allergen-specific subcutaneous immunotherapy (SCIT) practice in Mansoura university, a single center, large sample, randomized, controlled, two-parallel group study was conducted on 2197 patients with evidence of any of the respiratory allergic diseases such as allergic asthma, allergic rhinitis, allergic rhino-conjunctivitis and combined airway disease. 1997 patients received SCIT and 200 patients were treated with medication only (pharmacotherapy group) as a positive control. Clinical assessment using symptom scores and medication scores, spirometric lung function tests (forced expiratory volume at first second (FEV1)%, forced vital capacity (FVC)%, FVC/FEV1%) and skin prick tests was performed at baseline. Symptom scores and medication scores were collected during regular follow-up monthly visits along with follow-up lung function tests, after treatment. Out of the patients who received SCIT, 84.9% had an overall successful outcome with complete response in 44.2% (patients who reached maintenance dose with complete absence of allergy symptoms and discontinuation of medications) and partial improvement in 40.7%, whereas 15.1% showed no improvement. There was significant better efficacy of SCIT in cases with asthma alone than in cases with groups of combined airway diseases, and no significant difference in SCIT outcome between cases with asthma alone and cases with allergic rhinitis alone. There was significant better response to SCIT in males than in females and significant better response in the younger age group (5-20 y) than in the older ones. There were no significant differences in the outcome of SCIT in mono-sensitized versus poly-sensitized patients. No serious adverse reactions occurred after SCIT; local pain at injection site in 5.2% patients, grade 1 systemic reactions in 0.9% patients and grade 2 reactions in 1.25% patients were observed. Thus, it can be concluded that SCIT is an effective and safe treatment in selected cases of respiratory allergies.