BACKGROUND: It is unclear whether allergen immunotherapy (AIT) can be safely initiated during the pollen season (coseasonal initiation [CSI]) because of a potential increased risk of systemic allergic reactions. OBJECTIVE: To systematically review publications reporting the safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) CSI to validate or invalidate the perception of increased safety risk. METHODS: PubMed, EMBASE, Ovid, Literatura Latino Americana em Ciencias da Saude (LILACS), and Cochrane Library databases were searched without limits for studies of any design reporting SCIT or SLIT CSI for pollen allergen. Congress abstracts were included. RESULTS: Nineteen eligible studies were identified: 8 SCIT (n = 947 subjects total; n[340 double-blind placebo-controlled [DBPC]) and 11 SLIT (n = 2668 subjects total; n = 565 DBPC). Study characteristics and safety reporting were heterogeneous. No epinephrine administrations were reported. Discontinuation frequencies were 6% or less and 10% or less with SCIT and SLIT CSI, respectively. In SCIT studies, systemic allergic reaction frequency was 0% to 7% with "up to peak season" or CSI, 0% to 6% with "after peak season" or out-of-season initiation, and 0% to 7% with placebo. In SCIT studies, serious treatment-related adverse event (AE) frequency with CSI ranged from 0% to 2%; few severe AEs were reported. In SLIT studies, systemic allergic reaction frequency ranged from 0% to 4% with CSI, 0% with out-of-season initiation, and 0% to 2% with placebo. Overall, 2 serious treatment-related AEs with SLIT CSI were reported. Severe AE frequency in SLIT studies ranged from 0% to 8% with CSI, 0% to 12% with out-of-season initiation, and 0% to 8% with placebo. CONCLUSIONS: No increase in AEs of concern was observed with SCIT or SLIT CSI; however, additional data with standardized regimens and doses are needed. (C) 2016 American Academy of Allergy, Asthma & Immunology