Objective <p>To document the prevalence of parental alcohol and drug misuse (PADM) in infants’ first and subsequent child welfare cases, and to assess the risk of subsequent injury for infants exposed to PADM.</p> Methods <p>This study used linked Medicaid and child welfare system (CWS) data in Pennsylvania to identify all children born between 2016 and 2018 who had a confirmed CWS case by age one (<i>N</i> = 20,998). The injury analyses focused on children whose initial case included PADM and who were covered by Medicaid at birth (<i>N</i> = 11,180). Survival analyses and Cox Proportional Hazard models were used to assess risk of any physical harm, severe harm and head injuries among infants who remained in home following PADM exposure.</p> Results <p>Study documented that 64% of infants’ first cases included PADM. Infants with a PADM case who remained at home (versus entered care) were at increased risk of experiencing subsequent physical harm, severe physical harm, and head injuries. Few differences in harm outcomes were observed between infants with and without medically diagnosed prenatal substance exposure.</p> Conclusions <p>The Child Abuse Prevention and Treatment Act instructs medical professionals to create ‘plans of safe care’ for infants affected by substances, however, limitations in PADM identification as well as an insufficient public health response has resulted in many families not receiving the support and services needed. Coordinated efforts are needed to prevent, detect, and treat substance use disorders.</p>