This study reports on findings from the first two years of a study to compare a standard Life Skill Training (LST) program with an infused (I-LST) approach. Nine small, rural school districts were randomly assigned to LST, I-LST, or control conditions in grade seven. The LST program significantly reduced alcohol use, binge drinking, marijuana use, and inhalant use after one year for females, and the I-LST program significantly reduced smoking, binge drinking, and marijuana use for females. At the end of the second year the I-LST program continued to impact female smoking, but all other results were non-significant. There were no effects on males at either time point.