Until now, the basic treatment for food allergy has been to avoid the offending item. This approach is difficult in the case of common foods and in the case where there is a risk of severe reaction after consuming the offending food, even inadvertently. This is the follow-up of a previous study aimed at desensitizing 21 children with immunoglobulin E (IgE)-mediated cow's milk (CM) allergy. This protocol was totally or partially successful in 85% of cases, but failed in the remaining 15%. Our aims were to study the long-term effectiveness and safety of oral CM desensitization, and the prognostic value of Skin Prick Test (SPT) and specific serum CM IgE. The 21 children were called back (one dropped out). The allergic history and other information on CM intake over the last 4-5 yr were recorded. Children underwent SPT, and end-point SPT, with casein and alpha-lactoalbumin. Specific CM IgE was also measured. At follow-up, 14/20 children totally (n = 13, 65%) or partially (n = 1, 5%) tolerated CM. None of the recalled children reported use of emergency care. SPT positivity to casein and/or alpha-lactoalbumin decreased significantly (p < 0.01), and all the negative SPT referred to the tolerant children. Cutaneous sensitivity to both casein and alpha-lactoalbumin (end-point SPT) significantly decreased after the 6-month desensitization period of the previous study (p < 0.001), but did not decrease significantly at follow-up. A significant reduction of serum-specific CM IgE was also observed (p < 0.05). Clinical tolerance induced by oral CM desensitization persists in time. Negativization of SPT and reduction of specific CM IgE could be considered prognostic indicators of CM tolerance. Oral CM desensitization seems to be a promising method to treat CM food allergy. This protocol is time-consuming but offers the advantage that it can be performed at home. This methodology must only be used by trained staff.