This study examined interactive relationships among ethnic identity, gender, time in the US, and changes in substance use outcomes among a school-based sample of 1,731 Mexican-heritage preadolescents (ages 9-13). Residual change multilevel models adjusting for school clustering and using multiply imputed data assessed changes from beginning to end of fifth grade in use of alcohol, cigarettes, marijuana and inhalants, and four substance use antecedents. Effects of ethnic identity were conditional on time in the US, and in opposite directions by gender. Among males living longer in the US, stronger ethnic identity predicted desirable changes in all but one outcome (substance offers). Among females living longer in the US, stronger ethnic identity predicted undesirable changes in alcohol use, pro-drug norms, and peer substance use. Interpretations focus on differential exposure to substance use opportunities and the erosion of traditional gender role socialization among Mexican-heritage youth having lived longer in the US. (Contains 3 tables.)