Abstract Background The therapeutic strategy for children with cow’s milk allergy (CMA) consists in the elimination of cow’s milk (CM) from their diet. Donkey’s milk (DM) has been reported to be an adequate alternative, mainly to his nutritional similarities with human milk (HM) and excellent palatability. The aim of present prospective study was to evaluate the nutritional impact of DM on the diet of children with CMA in term of children growth. Methods Before the nutritional trial on children and during the study the health and hygiene risks and nutritional and nutraceuticals parameters of DM were monitored. Children with CMA were identified by the execution of in vivo and in vitro tests for CM and subsequent assessment of tolerability of DM with oral food challenge (OFC). Finally, we prescribed DM to a selected group of patients for a period of 6 months during which we monitored the growth of children. A total of 81 children, 70 with IgE mediated cow’s milk protein allergy (IgE-CMPA) and 11 with Food Protein Induced Enterocolitis Syndrome to CM (CM-FPIES), were enrolled. Results Seventy-eight out of 81 patients underwent the OFC with DM and only one patient with IgE-CMPA (1.5 %) reacted. Twenty-two out of 81 patients took part of the nutritional trial. All the 22 patients took and tolerated the DM, moreover DM did not change the normal growth rate of infants. Conclusions In conclusion, DM resulted safe in term of health and hygiene risks and nutritionally adequate: no negative impact on the normal growth rate of children was assessed. Therefore, it may be a suitable alternative for the management of IgE mediated CMA and FPIES, also in the first 6 months of life, if adequately supplemented.