OBJECTIVE: We tested the hypothesis that the gastrointestinal tolerance of a new infant formula equals or exceeds the tolerance of other milk-based infant formulas and compared the tolerance of this new formula with that of human milk. METHODS: This prospective, phase IV, open-label study was conducted in 17 countries. Healthy, full-term infants, 28 to 98 d old, were enrolled on their current feeding (no treatment assigned). Feeding regimens included human milk (HM), a new infant formula (NF; Similac Advance), other infant formula (OF), HM + NF, and HM + OF. Data for stool frequency, stool consistency, and gastrointestinal symptoms were collected in study diaries for 2 wk. RESULTS: Gastrointestinal tolerance was evaluated in 6999 infants: 979 (14.0%) received HM, 1695 (24.2%) received HM + NF, 635 (9.1%) received HM + OF, 2677 (38.2%) received NF, and 1013 (14.5%) received OF. Infants fed HM had softer and more frequent stools than did those who received NF, HM + NF, or OF (P < 0.001). Infants fed NF had softer and more frequent stools than did those fed OF (P < 0.001), including those fed Enfalac or S-26 (P < 0.001). Regurgitation (P < 0.001) and colic (P = 0.006) were more frequent with OF than with NF. All feeding regimens were well tolerated and only 3.5% of subjects experienced adverse events. CONCLUSIONS: This global study demonstrated that stools of infants fed NF are softer and more frequent than stools from infants fed OF and are closer to those of breast-fed infants. Infants consuming NF also experienced less regurgitation and colic than did infants in other feeding groups. Copyright © 2002 Elsevier Science Inc.