The Healthy Life in an Urban Setting (HELIUS) study is an ongoing prospective multi-ethnic cohort study, in Amsterdam, The Netherlands that started in 2011. The principle aim of the HELIUS study is to investigate the causes of (the unequal burden of) diseases across ethnic groups, with emphasis on mental disorders, cardiovascular disease and infectious disease, and their interrelationships. Stratified sampling by ethnic group was used to allow for an equal representation of the largest ethnic groups resulting in similar-sized samples of individuals of Dutch, African Surinamese, South-Asian Surinamese, Ghanaian, Turkish and Moroccan origin. A total of 24,780 individuals participated in the baseline examination that consisted of a questionnaire, physical examination and collection of biological material. Follow-up data have been collected through linkage with health care registries and a first follow-up data collection that took part between 2019 and 2022 and included 11,035 participants with an average follow-up time of 6.4 years. The data collection included information on demographics, medical history (including medication use and mental health status), anthropometrics, and fasting blood, urine and stool samples. Here we give an update on the HELIUS study and its methods regarding the first follow-up data collection, data linkage, and additional analyses using stored biomaterials. In addition, we provide a summary of key findings.