This document summarizes findings from the Center for Substance Abuse Prevention's National Cross-Site Evaluation of High-Risk Youth Programs, which identified characteristics associated with strong substance abuse prevention outcomes in 48 prevention programs. Major findings include: as youth age, levels of risk and protection shift considerably, with a steady movement from the protective to the risk conditions in most external and internal factors; gender plays an important role in risk, protection, and substance use (e.g., neighborhood conditions have a greater influence on substance abuse among males than females); connectedness protects against substance use (connectedness to family and school form the core of this protection); the peer environment is critically linked to substance use (youth whose peers do not use substance or whose peers disapprove of substance use report less use themselves); and broadening the range of protective influences in the external environments increases protection against substance use. (Contains 24 references and 15 figures.) (SM)