Objectives: Two factors were considered as predictors of children's risk for unintentional injury: (a) children's temperamentally difficult behavior patterns and (b) parenting. Along with hypotheses to replicate previous univariate effects, it was hypothesized that active, involved parents with sufficient time resources might reduce injury risk among temperamentally at-risk children. Methods: Study 1 used a retrospective design with a diverse sample of over 10,000 5-year-olds. Study 2 replicated Study 1 using a prospective design and behavioral data from a sample of over 1,000 children followed from 6 to 36 months of age. Results: In Study 1, male gender, child hyperactivity, and family poverty predicted injury in a univariate manner. In Study 2, male gender and lack of positive parenting predicted injury in a univariate manner. Interaction effects also emerged: in Study 1 the interaction between child hyperactivity and parental time resources protected children from injury, and in Study 2 the interaction between child's difficult temperament and positive parenting protected children from injury. Conclusions: Children at increased risk for injury, i.e., those with hyperactive and difficult behavior patterns, might be protected in the environment of positive parenting. Theoretically, results suggest that researchers should consider Temperament X Environment interactions along with univariate predictors of outcome behavior. From an applied perspective, results have implications for the design of injury prevention campaigns: Parents who spend positive time with temperamentally difficult children might protect them from injury.