Background: Multi-problem households (MPHs) are less physically active, eat less healthy, have higher perceived stress and worse self-reported health. A health promotion program was developed for MPHs targeting self-reported health, physical activity, healthy nutrition and engagement in social networks. This paper described the effectiveness of this program.Methods: A quasi-experimental study was conducted in the city Apeldoorn in the Netherlands with assessments at baseline and after six months. The primary outcome was self-reported health. Secondary outcomes were physical activity, fruit and vegetable consumption, social contacts, loneliness, mental health, BMI and lifestyle index. Data were analyzed with multilevel linear regression analyses.Results: A total of 116 respondents signed up for participation, of which 90 respondents (77.6%) completed the follow-up questionnaire. No differences were found between the control and intervention group on self-reported health (p=0.84). No differences were found between the groups on fruit consumption (p=0.34), but a significant interaction of group×time×health literacy was found (p=0.02). Follow-up analyses showed that only for participants with high health literacy significant differences in fruit consumption were found between control and intervention group at post-test (ß=8.059, p=0.02). No significant differences were found on other outcomes.Conclusions: Recruiting sufficient participants was a challenge. Significant differences in fruit consumption were found among individuals with a relatively high health literacy and none for the other primary and secondary outcome measures. Our outcomes indicate that health promotion programs, as well as their reachability, need to be further tailored to the needs of MPH.