The UNICEF/WHO Baby-Friendly Hospital Initiative suggests that breastfeeding activities in hospital are important to later breastfeeding. Understanding reasons for in-hospital supplementation may help to optimize the successful implementation of this initiative. The objective was to identify predictors of in-hospital initial formula supplementation of healthy, breastfeeding newborns. The authors analyzed 564 Canadian mother-infant pairs and interviewed nurses. Half of the study infants (47.9%) received formula in hospital; the median age at first supplementation was 8.4 hours. Risk for supplementation was affected by birth occurring between 7 PM and 9 AM (hazard ratio [HR] varied with time) and high maternal trait anxiety (HR=1.61, 95% confidence interval [CI]=1.01, 2.59). The following variables were protective against supplementation: planning to exclusively breastfeed (HR=0.46, 95% CI=0.33, 0.64), planning to breastfeed for >or=3 months (HR=0.56, 95% CI=0.37-0.86), childbirth education (HR=0.61, 95% CI=0.43, 0.86), mother born in Canada (HR=0.68, 95% CI=0.53, 0.87), completion of community college (HR=0.76, 95% CI=0.59, 0.98), male infant (HR=0.78, 95% CI=0.61, 0.99), and breastfeeding at delivery (HR varied with time). Nurses reported breastfeeding problems, infant behavior, and maternal fatigue as reasons for supplementing. Reassessing patterns of night feeds and encouraging breastfeeding at delivery may decrease supplementation. Trait anxiety reduction and the role of infant gender in supplementation merit further study.