Introduction: Subcutaneous immunotherapy (SCIT) is the oldest and an efficient immunotherapy method that has been used for the treatment of allergic diseases. Systemic adverse effects (SAEs) may occur during the SCIT. For this reason, there may be problems in the continuing treatment. In this study, we primarily aimed to determine the frequency of SAEs, the risk factors that may be associated with SAEs, and clinical and laboratory parameters that can predict systemic reactions in the patients who underwent SCIT. Second, we aimed to evaluate the reasons for discontinuing SCIT and the conditions special to Turkey. Methods: The files of 295 patients who had received SCIT were evaluated retrospectively. Results: SCIT was administered against house dust mites (HDM) in almost all patients (n: 291, 98.6%). A total of 14,357 injections were administered to 295 patients included in the study, and 47.8% (n: 141) of the patients discontinued treatment. The most common reason for discontinuing treatment was the supply problem in Turkey for immunotherapy preparations (n: 70, 49.6%). The second reason was that the injection visits were not continued regularly, even though there were no adverse effects related to the treatment (n: 44, 31.2%). SAEs were observed in 16.6% of the patients and 0.66% of the injections. SAEs were more frequent in girls, in asthmatic patients, and in moderate asthmatic patients (p = 0.005, p = 0.016, p = 0.043, respectively). Treatment was terminated in 13 patients (4.4%) due to SAEs. The most common SAE was bronchoconstriction (n: 40, 85.1%). None of our patients developed hypotension or loss of consciousness. Median blood eosinophil count and basophil count and the skin prick test diameter for Dermatophagoides farinae were observed to be significantly higher in the group with SAE (p = 0.024, p = 0.034, p = 0.045, respectively). Conclusion: Although SAE may develop in pediatric patients undergoing HDM-specific SCIT, severe reactions are rare. Girls, asthmatic patients, especially moderate asthmatic patients, and patients with high blood eosinophil and basophil levels should be monitored more carefully for the development of SAE.