Introduction: There is a strong socioeconomic gradient in health care costs. However, little is known about the role of lifestyle factors in the association between health care costs and socioeconomic status (SES). This study investigates variation in the association between lifestyle indicators and health care costs between and within neighborhoods with similar SES. Method: Using 2016 whole-population data for all 790 neighborhoods of the Netherlands, we estimated the association between neighborhood average health care cost performance (i.e., health care costs adjusted for population age and gender) and neighborhood socioeconomic status (NSES) and four lifestyle indicators smoking, alcohol consumption, exercise and sport club membership. Additionally, using regression analysis, we explored the multivariate relationship between average health care cost performance, NSES and lifestyle indicators. Results: Neighborhoods with proportionally fewer smokers and more sport club members had significantly lower average health care costs. Remarkably, neighborhoods with more people who complied with the recommended maximum alcohol consumption had significantly higher health care costs. These findings were consistent within and between neighborhoods with different SES levels. Neighborhoods with more compliance with exercise guidelines had lower health care costs. However, this relationship was inconsistent across different NSES levels, with the largest cost reductions found in the most deprived neighborhoods. Conclusion: Our findings suggest that prevention policies aimed at reducing the number of smokers and increasing sport club membership may reduce health care costs across all NSES groups, while increasing compliance with physical exercise norms may be effective mainly in low SES neighborhoods.