Lactose has beneficial nutritional effects in infancy, particularly on calcium retention and on Bifidobacterium colon microflora development. OBJECTIVE The objective of this controlled, prospective, randomized double-blind study was to assess the adequacy and safety of an infant formula containing only lactose as carbohydrate, as compared to a usual formula. METHODS Healthy non-breast-fed infants aged under 7 days were randomized to be fed exclusively with a conventional formula containing lactose (9.6 g/100 kcal) and maltodextrin (1.6 g/100 kcal) or the isocaloric-isoprotein study formula containing 100% lactose (11.2 g/100 kcal) for 120 days. Primary outcome was daily weight gain at D0 and D120. Weight, length, body mass index, formula consumption, tolerance, and safety were assessed monthly. The non-inferiority of the study formula was rejected if the difference in weight gain was higher than 2.5 g/day in the control group. RESULTS One hundred and seventy-eight infants were enrolled. Mean daily weight gain in the study group differed by 0.71 g/day (95% CI: -2.23; 0.82) indicating the non-inferiority of the study formula. Growth was normal and similar in the two groups, but formula intake was decreased in the study group, leading to a decrease in energy and protein intakes. Tolerance was good and adverse events did not differ between the two groups. CONCLUSIONS The 100% lactose study infant formula was safe and non-inferior to a conventional formula in ensuring normal growth during the first 4 months of life.