Home injuries are an important public health issue in both developed and developing countries. This study focused on the Italian epidemiological framework between 1999 and 2006, using a nation-representative sample provided by the National Institute of Statistics. Every year, about 3,000,000 Italian residents reported at least one home injury, with an overall annual rate of 5.2/100 (95% CI 5.1–5.4); 3.2/100 (3.0–3.4) for males and 7.2/100 (6.9–7.4) for females. Poisson regression models were used for different age-specific populations (children, young/adults and older people), to evaluate the effects of socio-demographic, health/income satisfaction and housing variables. For children, non-applicable variables (including smoking and health satisfaction) were taken as those of the head of family, while housework time was taken the family mean time. Evidence of decreasing time trend in risk of home injury was found only among young/adults (p < 0.01). The following were risk factors: female gender (adjusted relative risk—RR 2.0 for older people and RR 1.9 for young/adults, p < 0.01); one additional hour of work at home (RR 1.009, p < 0.01 for young/adults and RR 1.016, p = 0.01 for children); smoking (RR 1.3, p < 0.01 for young/adults and p = 0.02 for children); health dissatisfaction (RR 1.3, p = 0.05 for children, RR 1.6 for young/adults and RR 1.7 for older people, p < 0.01); income dissatisfaction (RR 1.2, p < 0.01 for young/adults ); living alone (RR 1.5, p < 0.01 for young/adults and RR 1.2, p < 0.02 for the older people); having a garden (RR 1.1, p < 0.01 for young/adults ). Awareness of the need for safety at home could be boosted by information campaigns on the risk, and its social cost could be reduced by specific prevention schemes. Developing tools for assessing the risk at home and for removing the main hazards would be useful for both informative and prevention interventions.