Abstract Background In the Netherlands, the HPV-vaccine uptake was 52% during the 2009 catch-up campaign (birth cohorts 1993–1996). This increased to 61% in the regular immunization program (birth cohorts 2000–2001). However for birth cohorts 2003–2004 the uptake declined to 45.5%. With this study we aimed to gain insight into social, economic and cultural determinants that are associated with HPV-vaccination uptake and which subgroups with a lower HPV-vaccination uptake can be identified. In addition, we investigated whether the influence of these factors changed over time. Methods To study the determinants of HPV-vaccine uptake we performed a database study using different aggregation levels, i.e. individual level, postal code level and municipality level. All Dutch girls who were invited for HPV-vaccination through the National Immunization Program in the years 2012, 2014 and 2017 (i.e. birth cohorts 1999, 2001 and 2004, respectively) were included in the study population. We conducted multilevel logistic ...