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Many college entrants’ parents do not have college degrees. These entrants are at high risk for attrition, suggesting it is critical to understand mechanisms of attrition relative to parental education. Moderators and mediators of the effect of parental education on attrition were investigated in 3,290 students over 4 years. Low parental education was a risk for attrition; importantly, college GPAs both moderated and mediated this effect, and ACT scores, scholarships, loans, and full-time work mediated this effect. Drug use, psychological distress, and few reported academic challenges predicted attrition, independent of parental education. These findings might inform interventions to decrease attrition.