We evaluated the efficacy and safety of oral immunotherapy (OIT) combined with 24 weeks of omalizumab (OMB) at inducing desensitization in children with cow's milk allergy (CM) compared with an untreated group. The present study was a prospective randomized controlled trial. Sixteen patients (age, 6-14 years) with high IgE levels to CM were enrolled in the present study. Patients were randomized 1:1 to receive OMB-OIT group or untreated group. The primary outcome was the induction of desensitization at 8 weeks after OMB was discontinued in OMB-OIT treated group and at 32 weeks after study entry. None of the 6 children in the untreated group developed desensitization to CM while all of the 10 children in the OIT-OMB treated group achieved desensitization (P < 0.001). A significantly decreased wheal diameter in response to a skin prick test using CM was found in the OMB-OIT treated group (P < 0.05). These data suggest that OIT combined with OMB using microwave heated CM may help to induce desensitization for children with high-risk CM allergy. This prospective randomized controlled trial was intended for 50 participants but was prematurely discontinued due to overwhelming superiority of OMB combined with microwave heated OIT over CM avoidance.