As there have been few science-based evaluations of secondary prevention programs, the Federal Office of Public Health in Switzerland carried out a national program evaluation at 12 sites in the French- and German-speaking parts of Switzerland to study the question, "What works in secondary prevention?" These 12 centers offer different forms of assistance for young people aged 11 to 20 years old. The five types of center are distinguished according to their structure and the amount of time spent with each youth. The design of the study is quasi-experimental with intervention and comparison groups. Up to now, 1,400 youth have been involved in the 12 centers. The intervention lasts about 6 months. Data are collected on entry, at program completion, and at 12- and 24-months post intervention. One of the main findings is that even "hard to reach" youths have a chance to be integrated in school, undertake vocational training, or to secure employment. More than 70% of all youths were integrated or re-integrated. The results of the study are presented in effect sizes (ES). Effects on mental health and substance use outcomes are contradictory and vary by age and gender of client, and by type of center. In general, effects on mental health outcomes are greater than for other variables such as substance use and self-concept, and they are greater for more symptomatic youths and for boys rather than girls. The authors conclude with proposals for ways to enhance program effectiveness and targeted assessment. (Contains 13 tables and 1 figure.)