A 3-year prospective post marketing survey on the safety of the recently developed ultrashort pre-seasonal subcutaneous immunotherapy (uSCIT-MPL4) with pollen allergoids adjuvanted with monophosphoryl lipid A was performed. A total of 510 patients received uSCIT-MPL4, 61% for grass, 35.7% for birch, 13.2% for parietaria and 3% for other pollens (ragweed, mugwort, and olive). A total of 3308 injections were given and the mean duration of uSCIT-MPL-4 was 2.3 years. Overall, only 7 slight systemic reactions (SR) were observed in 510 patients (1.37%) and 2.11/1000 injections suggesting that this treatment is even safer than traditional depot injection SIT.