Background In the last couple of years, genome-wide association studies have largely altered the scope in genetic research in diseases in which both environmental and genetic risk factors contribute to the disease. To date, the genetic risk loci identified in stroke have lagged behind those in other complex diseases, possibly because of the heterogeneity of stroke phenotypes. Sufficiently large cohorts with well-defined and detailed phenotyping of stroke patients are needed to identify additional genetic risk loci. Design The String-of-Pearls Institute is a unique partnership between all eight University Medical Centers in the Netherlands. It was established in 2007 by the Netherlands Federation of University Medical Centers, and it conducts a large prospective cohort study in which comprehensive clinical data, detailed phenotyping of stroke, imaging data, and biomaterials are collected in a large cohort of stroke patients. Aims The study aims (1) to collect a sufficiently large prospective cohort of stroke patients, with well-defined phenotypes; (2) to collect blood samples and DNA in a standardized infrastructure, allowing for storing and analyzing the samples in a uniform way; (3) to investigate associations between genetic risk loci and stroke; (4) to create possibilities to perform epidemiological studies in a well-defined hospital-based cohort of stroke patients; and (5) to allow for pooling data with other large ongoing genetic stroke studies.