The PopGen biobank was established in 2003 for research into the genetic risk factors for complex diseases. In addition to specific patient groups, a random sample from the general population was recruited as well. This cross-sectional study was mainly used as a control sample in genetic-epidemiological research. Recently, this part of the biobank was developed further into a prospective cohort study to investigate longitudinal changes of inflammatory biomarkers. Between 2005 and 2007, 1,317 study participants (age: 19-77 years, 55% men) were recruited into the PopGen control cohort, 747 via the local population registry and 570 as blood donors. Baseline assessment comprised a questionnaire, a medical examination, sampling of blood as well as ad hoc analyses of a range of biomarkers and genetic factors. Beginning in 2010, all study participants were re-invited for a program that was expanded by a food frequency questionnaire, collection of urine and stool samples, and an offer of magnetic resonance imaging to capture body fat distribution. The current response proportion is approximately 70%. The development of the PopGen controls into a prospective cohort study was originally driven by biomarker research questions, for instance related to chronic inflammation. Future follow-up will now also enable research into the influence of lifestyle variables.