A newborn screen designed to predict family risk was examined to: (a) determine whether all families with newborns were screened; (b) evaluate its predictive validity for identifying risk of out-of-home placement, as a proxy for maltreatment; (c) determine which items were most predictive of out-of-home placement. All infants born in Manitoba, Canada from 2000 to 2002 were followed until March 31, 2004 (N = 40,886) by linking four population-based data sets: (a) newborn screening data on biological, psychological, and social risks; (b) population registry data on demographics; (c) hospital discharge data on newborn birth records; (d) data on children entering out-of-home care. Of the study population, 18.4% were not screened and 3.0% were placed in out-of-home care at least once during the study period. Infants not screened were twice as likely to enter care compared to those screened (4.9% vs. 2.5%). Infants screening at risk were 15 times more likely to enter care than those screening “not at risk.” Sensitivity and specificity of the screen were 77.6% and 83.3%, respectively. Screening efforts to identify vulnerable families missed a substantial portion of families needing support. The screening tool demonstrated moderate predictive validity for identifying children at risk of entering care in the first years of life.