Background  Extensively hydrolyzed formulas are recommended for the dietary management of infants with cow's milk allergy (CMA). Objectives Hypoallergenicity, growth, and gastrointestinal (GI) tolerability of a new extensively hydrolyzed whey‐protein formula (eHWF) in CMA children were assessed. Methods In this prospective, randomized, international, multi‐center study (Trial NL3889), 34 children with confirmed CMA (74% IgE‐mediated) underwent a double‐blind, placebo‐controlled food challenge (DBPCFC) with an eHWF developed with non‐porcine enzymes, supplemented with prebiotic short‐chain galacto‐ and long‐chain fructo‐oligosaccharides (0.8 g/L, ratio 9:1), arachidonic acid (0.35/100 g), and docosahexaenoic acid (0.35/100 g). If tolerant to the eHWF, children participated in a 7‐day open food challenge with this eHWF. Anthropometrics and GI tolerability were assessed in an optional 16‐weeks follow‐up. Results Of the 34 children who started the DBPCFC with the eHWF, 25 subjects (19 boys, mean age: 61 weeks, 18 with IgE‐mediated CMA) completed the DBPCFC and 7‐day open challenge without major protocol deviations and tested negative at both challenges. One child experienced a late moderate eczematous allergic reaction in the optional follow‐up period, indicating the need for close monitoring of subjects starting new formula. Weight and length gain followed the World Health Organization growth curves. Changes in frequency and consistency of stools upon test formula intake were transient. Conclusions The newly developed eHWF is a suitable option in CMA treatment as all subjects tolerated the product. This result is in line with the international criteria for hypoallergenicity (American Academy of Pediatrics) that state that more than 90% of CMA children must tolerate the formula. Use of the formula is also associated with normal growth curves and GI tolerability. Trial registration Trial NL3889, https://www.trialregister.nl/trial/3889.