Background: The Happiness Route is an innovative intervention that uses a happiness-based approach for people with an accumulation of risk factors for low well-being: socially isolated people with health impairments and a low socioeconomic status. The goal of this intervention is to improve well-being by engaging participants in intrinsically motivated activities with methods from positive psychology. We hypothesize that the primary outcome measure, emotional, social and psychological well-being of participants of the Happiness Route, will increase in comparison to the traditional and commonly-used problem-based approach. Secondary outcome measures are health-related quality of life, psychosocial functioning and health care consumption. Methods and desig: Participants will be socially isolated people with health problems and a low socioeconomic status. Participants will be recruited in ten Dutch communities and candidates will be signed up by intermediaries, professionals from the health and social sector. Randomly assigned, half of the participants will follow the Happiness Route and half of the participants will follow the active, problem-focused control group ‘Customized Care’. In total, 256 participants will be included. In both conditions, participants will receive counseling sessions from trained counselors. In the control group, participants will talk about their problems and the care they get and counselors help to optimize their care. In the Happiness Route, the counselor ask questions such as “How do you want to live your life?”. The intervention helps people to find their ‘passion’, i.e., a positive goal-engaged and intrinsically motivated activity. It enables them to follow their passion through by a once-only personal happiness budget (maximal €500). We use well-validated and reliable questionnaires to measure primary and secondary outcome measures at baseline, directly after the intervention and at a nine-month follow-up. Discussion: Shortcomings of earlier intervention studies in positive psychology will be tackled with this study, such as having a target group who is especially vulnerable for low well-being. The practice-based setting is especially interesting, as it can give valuable insights in how positive psychology interventions work in practice, but can also give rise to several challenges.