The present study evaluated long-term effects of a home-based smoking prevention program targeting smoking-specific parenting in families with children with and without asthma. A total of 1398 non-smoking children (mean age 10.1) participated, of which 197 (14.1%) were diagnosed with asthma. Families were blinded to group assignment. The intervention group (n = 684) received booklets with assignments that actively encouraged parents to engage in smoking-specific parenting strategies. Control families (n = 714) received booklets containing basic information about youth smoking. Latent growth curve modeling was used to calculate intercepts and slopes to examine whether there was change in the different parenting aspects over the study period. Regression analyses were used to examine whether a possible change was different for intervention and control condition families with and without a child with asthma. For those smoking-specific parenting aspects that changed over time, families in the intervention and control condition increased similarly. Families with a child with asthma did not engage in parenting at higher levels due to the intervention program than parents of non-asthmatic children. This prevention program did not affect smoking-specific parenting in the Netherlands. Future prevention research could focus on other risk factors for smoking initiation among adolescents with asthma.