Objectives: To test the efficacy of a brief intervention based on Motivational Interviewing in proactively recruited general hospital patients randomly allocated to an intervention or a control group. Methods: Patients aged 18 to 69 years are proactively recruited in surgical and internal wards of two general hospitals in the northern German city of Lübeck. Patients with regular use of prescription drugs in the last three months and/or prescription drug dependence or -abuse are randomly assigned to two conditions: (1) an intervention group with two counseling sessions based on Motivational Interviewing plus one individualized feedback based on the Transtheoretical Model of behavior change (TTM) or (2) as usual care. Outcome measures are reduction or discontinuation of prescription drug use and utilization of formal help. The efficacy of the intervention will be examined within a 3 and a 12 month follow up.