Real world implementation of proactive screening and brief intervention in health care is threatened by high cost. Using e-health interventions and screening for multiple health risk factors may provide more efficiency. We describe methodological details of a proactive multipurpose health risk screening in health care settings and report on participation rates, participants' characteristics, and participation factors. Patients between 18 and 64years from ambulatory practices and hospitals were proactively approached by study assistants at three sites for a computerized screening on harmful alcohol and tobacco consumption, depressive symptoms, insufficient fruit/vegetable consumption, physical inactivity and overweight. On the basis of their health risk pattern, a computerized algorithm allocated patients to one of five studies each of them addressing a psychiatric research question. Among all eligible patients, 13,763 (86.5%) were screened. Younger age and being female predicted screening participation. Of those with complete data (n=12,828), 82.9% reported at least two health risks and 34.0% were eligible for a study. Study participation ranged between 35.2% and 50.8%, and was associated with socio-demographics and problem severity. This study supports the use of systematic proactive screening for multiple health risks in health care settings as it is more resource-saving than single focused screening.