A high protein intake in early life is associated with a risk of obesity later in life. The essential amino acid requirements of formula-fed infants have been reassessed recently, enabling a reduction in total protein content and thus in protein intake. We aimed to assess the safety of an infant formula with a modified amino acid profile and a modified low-protein (mLP) content in healthy term-born infants. Outcomes were compared with a specifically designed control (CTRL) infant formula. In this double-blind, randomized controlled equivalence trial, infants received either mLP (1.7 g protein/100 kcal; n=90) or CTRL formula (2.1 g protein/100 kcal; n=88) from enrollment (age≤45 d) to 6 mo of age. A breastfed group served as a reference (n=67). Anthropometry and body composition were determined at baseline, 17 wk (including safety blood parameters), and 6 mo of age. The primary outcome was daily weight gain from enrollment up until the age of 17 wk (at an equivalence margin of ±3.0 g/d). Weight gain from baseline (mean±SD age: 31±9 d) up to the age of 17 wk was equivalent between the mLP and CTRL formula groups (27.9 and 28.8 g/d, respectively; difference: -0.86 g/d; 90% CI: -2.36, 0.63 g/d). No differences in other growth parameters, body composition, or in adverse events were observed. Urea was significantly lower in the mLP formula group than in the CTRL formula group (-0.74 mmol/L; 95% CI: -0.97, -0.51 mmol/L; P<0.001). Growth rates, fat mass, fat-free mass, and several essential amino acids were significantly higher in both formula groups than in the breastfed reference group. Feeding an infant formula with a modified amino acid profile and a lower protein content from an average age of 1 mo until the age of 6 mo is safe and supports an adequate growth, similar to that of infants consuming CTRL formula. This trial was registered at www.trialregister.nl as Trial NL4677.