Aims: To compare the growth, safety, and tolerance acquisition in infants with cow's milk protein allergy (CMPA) when fed a hydrolyzed rice formula (HRF) versus an extensively hydrolyzed milk protein formula (EHF). Methods: A prospective, multicenter, randomized, double-blind, controlled trial was conducted with infants diagnosed with CMPA, both IgE-mediated and non-IgE-mediated (up to grade II anaphylaxis). Infants were assigned to receive either a HRF or an EHF over a 12-month follow-up period. The primary outcomes assessed were anthropometric measurements and safety. Infants who had a negative Open Oral Food Challenge (at 6, 9, and 12 months) were allowed to transition to a standard milk formula. Compliance, tolerability, and adverse events (AEs) were also evaluated. Results: A total of 105 children from six centers were enrolled in the study. Measurements of weight, length, weight-for-length, BMI, and head circumference z-scores indicated normal growth, with no significant differences between the HRF and EHF groups at baseline or during follow-up visits. Additionally, triceps skinfold thickness, mid-arm circumference, and arm muscle area showed no significant differences between the groups. Overall, 29 product-related adverse events were reported (12 in the HRF group and 17 in the EHF group). Five children in the HRF group and eleven in the EHF group experienced serious adverse events; none were attributed to the intervention. There was a trend toward faster acquisition of tolerance in HRF-fed infants compared to EHF-fed infants, but this did not reach statistical significance (median age 20.4 months versus 16.3 months, respectively, p=0.1753). Conclusions: Both EHF and HRF demonstrated appropriate growth, acquisition of tolerance, and a good safety profile in infants with CMPA, with no significant differences between the formulas.