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During the past twenty years, an increasing percentage of grandparents have assumed the responsibility for raising their grandchildren, and there are currently over 2.5 million custodial grandparents in the United States (Census, 2003). Significant research has examined the effects of caregiving on custodial grandparents, and found that custodial grandparents experience decreased well-being, and report more stressors than their peers (Hayslip, Kaminski & Earnheart, 2005). One area that has not been well-examined is the effect of being raised by grandparents on grandchild well-being, particularly injury prevention. The safety of these home environments is of importance, as unintentional injury is the leading cause of death across all age groups (Borse et al., 2008). A model was proposed for the prediction of custodial grandchild safety based on grandparent factors, with the predictors of gender, safety knowledge, and depressive symptoms. Our results suggested an adequate fit of the data to the model [X2 (df = 11, n = 144) = 33.57, p < .001; GFI = .939; CFI = .932; RMSEA = .120)], and the model explained 21.9% of the variance in child injuries, 25.4% of the variance in safety knowledge, and 39.8% of the variance in home hazards. Several gender differences were also present, for both grandparent and grandchild gender. Custodial grandfathers reported less safety knowledge, more hazards within their homes, more child injuries than grandmothers. Grandparents of grandsons reported less safety knowledge, more home hazards, and more child injuries than those raising girls. Implications, limitations, and future directions are discussed.