Subcutaneous immunotherapy (SCIT) is a well-established treatment modality for allergic patients that has been successfully used for many decades. Sublingual immunotherapy (SLIT) was introduced over the last 20 years as a safer alternative to SCIT with no single case of mortality has ever been reported with it. The aim of this study was to evaluate the efficacy and safety of SLIT versus SCIT in treating respiratory allergic patients. This study was a non-randomized controlled trial including 72 patients suffering from respiratory allergy to house dust mites (HDM) (Dermato-phagoidesfarinae and Dermato-phagoide-spteronyssinus) and date palm pollen (Phoenix dactylifera, Pho). The patients were subjected to full detailed allergy history taking, symptoms and medication scores calculation, skin prick test, Peak Expiratory Flow Rate (PEFR) for asthmatic patients, specific IgE test for HDM allergen. Patients received either SLIT or SCIT, then symptoms and medication scores, PEFR and specific IgE for HDM allergen were reassessed after 6 months of immunotherapy. Any adverse reactions were also recorded. The results showed that patients received either SLIT or SCIT showed a highly significant improvement in symptoms and medication scores with a highly significant improvement in PEFR, while specific IgE levels were not significantly changed. Local adverse reactions were noticed only with SCIT. We conclude that both modalities of treatment were equally effective in treatment of respiratory allergic patients to house dust mites and date palm pollen but SLIT had a more safety profile than SCIT.