Screening and referral for substance use are essential components of prenatal care. However, little is known about barriers to participation in substance use interventions that are integrated within prenatal care. Our study examines demographic and clinical correlates of participation in an initial assessment and counseling intervention integrated into prenatal care in a large healthcare system. The sample comprised Kaiser Permanente Northern California pregnant women with a live birth in 2014 or 2015 who screened positive for prenatal substance use via a self-reported questionnaire and/or urine toxicology test given as part of standard prenatal care (at ~ 8 weeks gestation). Of the 11,843 women who screened positive for prenatal substance use (median age = 30 years; 42% white; 38% screened positive for alcohol only, 20% for cannabis only, 5% nicotine only, 17% other drugs only, and 19% ≥ 2 substance categories), 9836 (83%) completed the initial substance use assessment and counseling intervention. Results from multivariable logistic regression analyses indicated that younger age, lower income, single marital status, and a positive urine toxicology test predicted higher odds of participation, while other/unknown race/ethnicity, greater parity, receiving the screening later in pregnancy, and screening positive for alcohol only or other drugs only predicted lower odds of participation (all Ps < .05). Findings suggest that integrated substance use interventions can successfully reach vulnerable populations of pregnant women (e.g., younger, lower income, racial/ethnic minorities). Future research should address whether differences in participation are due to patient (e.g., type of substance used, perceived stigma) or provider factors (e.g., working harder to engage traditionally underserved patients).