The aim of this study was to evaluate the safety and efficacy of oral rush desensitization in children with cow milk allergy.Prospective study. We included IgE-mediated cow milk allergy children over 3 years in 3 Spanish hospitals. Increasing doses of cow milk for 5 days from 1 cc of 1% to 200 cc of pure milk were administered. Clinical follow-up was conducted and we compared specific IgE levels at onset, 6, 12 and 24 months after desensitization.We included 18 children (13 males) between 3 and 14 years (mean 5.96). A total of 271 doses were administered; there were 55 adverse reactions (84% mild). At the end of the protocol, 100% showed some degree of tolerance (39% total). Full tolerance was achieved in 72% of patients after two years. Two children failed to achieve tolerance. There was a significant decrease in the levels of specific IgE to cow milk and alpha-lactalbumin at 24 months, and to casein at 6, 12 and 24 months, compared to baseline.Oral rush desensitization is a safe and effective therapeutic option for patients with persistent cow milk allergy to medium term.