Background: Subcutaneous allergen immunotherapy (SCIT) is a very effective treatment modality; however, it can be associated with both local and systemic reactions (SR). Identifying patient factors that predict SR remains paramount. Objective: Our aim was to identify the rate of SRs to SCIT as well as identify patient risk factors associated with the development of SRs. Methods: We conducted an institutional review board approved 10-year retrospective chart review of 459 patients who received SCIT in our clinic. The patients were placed into cohorts according to age, which included pediatric (5-18 years), adult (19-64 years), and senior (>65 years) patients. Results: An SR (N = 177) was identified in 24.8% of the patients (n = 114). The incidence of SR per injection was 0.2% (177 SRs of 74,183 total injections). SRs were identified as class 1 (n = 152), class 2 (n = 21), class 3 (n = 2), and class 4 (n = 2) according to the 2010 World Allergy Organization's SR grading system. There were no observed differences in the number of SRs with respect to age group. Female patients were more likely to have an SR (p = 0.02) overall as well as more than one reaction (p = 0.002). Other risk factors included the following: a patient-reported history of food allergy (p = 0.05), drug allergy (p = 0.005), or positive skin test result to cat and/or dog (p = 0.01). In addition, patients who were receiving SCIT to cat and/or dog (p = 0.004) or to dust mite (p = 0.03) were more likely to have an SR. Conclusion: In our patient population, the majority of SRs to SCIT occurred in female patients, patients with a history of drug or food allergies, and those who were receiving pet or dust-mite SCIT.