This article examined the impact of linguistic acculturation and gender on the substance use initiation of a sample of 1,473 Mexican heritage preadolescents attending 30 public schools in Phoenix, Arizona. It was hypothesized that linguistic acculturation operates differently as a risk or protective factor for young children than for older youth. The study used discrete-time event history methods to model the rate at which nonusing children initiate substance use. Alcohol, cigarettes, marijuana, and inhalants were studied separately while inhalant use was examined more closely. Results suggested that while linguistic acculturation is a risk factor for Mexican heritage preadolescents, this association depended on gender, the linguistic acculturation context (family, friends, or media), and the type of substance. For inhalants, higher linguistic acculturation with friends was inversely associated with drug initiation both for boys and girls. Implications for preventive science and future intervention research are discussed. (Contains 5 tables.)