AbstractHealthcare costs in the Netherlands are rising and vary considerably among regions. Explaining regional differences in healthcare costs can help policymakers in targeting appropriate interventions in order to restrain costs. Factors usually taken into account when analyzing regional differences in healthcare costs are demographic structure and socioeconomic status (SES). However, health, lifestyle, loneliness and mastery have also been linked to healthcare costs. Therefore, this study analyzes the contribution of health, lifestyle factors (BMI, alcohol consumption, smoking and physical activity), loneliness, and mastery to regional differences in healthcare costs. Analyses are performed in a linked dataset (n = 334,721) from the Dutch Public Health Services, Statistics Netherlands, the National Institute for Public Health and the Environment (year 2016), and the healthcare claims database Vektis (year 2017) with Poisson and zero-inflated binomial regressions. Regional differences in general practitioner consult costs remain significant even after taking into account health, lifestyle, loneliness, and mastery. Regional differences in costs for mental, pharmaceutical, and specialized care are less pronounced and can be explained to a large extent. For total healthcare costs, regional differences are mostly explained through the factors included in this study. Hence, addressing lifestyle factors, loneliness and mastery can help policymakers in restraining healthcare costs. In this study, the region of Zuid-Limburg represents the reference region. Use compare regions for health and healthcare costs (Regiovergelijker gezondheid en zorgkosten) in order to select all other Dutch regions as reference region.