Objective: To assess the effect of maternal prenatal and past-year cocaine use on mother-child interactions across preschool years. Methods: The sample is drawn from the Miami Prenatal Cocaine Study, a longitudinal follow-up of prenatal cocaine exposure (PCE) in a large cohort of African-American infants prospectively enrolled at birth. Analyses are based on the 366 children (168 PCE and 198 non-cocaine-exposed) in the care of their biological mothers and with completed mother-child interaction measures at the 3- and/or 5-year assessments. Videotaped interactions were coded using a modified Egeland Teaching Task scheme. Generalized linear models with a generalized estimating equations approach were used to evaluate the effect of PCE on the overall quality of maternal-child interaction, measured by the Egeland total score at both study visits, and on the individual Egeland subscales at the 5-year visit, while adjusting for other suspected influences on interactions. Results: PCE dyads demonstrated less optimal overall mother-child interactions compared with non-cocaine-exposed dyads. The estimated PCE-associated difference did not shift appreciably with statistical adjustment for child sex, child age at examination, or other birth covariates. PCE dyads with past-year maternal cocaine use had significantly lower Egeland summary scores compared with children with neither exposure. In subscale analyses, PCE was most strongly associated with greater maternal intrusiveness and boundary dissolution at the 5-year visit. Conclusions: Prenatal and past-year maternal cocaine use seems to be associated with poorer quality in mother-child interaction during early childhood. These dynamics should be considered when examining the association between PCE and child cognitive, behavioral, and academic outcomes.