Childhood abuse and partner violence are associated with prenatal substance abuse, but the potential impact of current family discord, which reflects broader family relationships and encompasses problems less severe than violence, has had little evaluation in pregnant substance users. Using data from 196 pregnant substance users participating in a NIDA Clinical Trials Network randomized clinical trial, we examined the relationship of baseline family discord to substance use and treatment session attendance. Family discord was assessed using items from the family composite of the Addiction Severity Index. Substance use was assessed by the Substance Use Calendar and urine drug screens (UDS). Assessments were weekly for four weeks and at two- and four-month post-randomization. Women with family discord were more likely to report living with a problematic substance user, reported a higher percentage of substance use days throughout each study phase, had a greater proportion of positive UDS over the four-month study period, and attended more weeks of treatment during the first month. Specific treatment interventions targeting pregnant women with family discord may be warranted.