Objectives: The purpose of this study was to estimate the prevalence of Healthy People 2010 disease conditions in a large population-based cohort in central Wisconsin (WI, USA) and to consider how these conditions can be prioritized for research based on the use of healthcare services, the prevalence of various disease states and the resulting study power. Methods: Healthy People 2010 diagnoses were estimated for participants in the Personalized Medicine Research Project (PMRP), a large population-based biobank for residents aged 18 years and older living in central Wisconsin. By interrogating the electronic medical record, three parameters were calculated for each diagnosis: mean number of concomitant diagnoses, mean number of annual clinic visits before diagnosis and mean number of clinic visits after diagnosis. Results: A total of 18,239 adults enrolled in PMRP from September 2002 to May 2005 and were included in the study. They had a mean age of 49 years (standard deviation: 18.5), ranging from 18–98 years; 57% were female. At least one Healthy People 2010 disease was diagnosed in 86.4% of the participants; 13.6% had never been diagnosed with any of these conditions. The median number of diagnoses per subject was three (range: 1–15). The median number of annual visits after diagnosis was lowest for chronic obstructive pulmonary disease (9.1) and highest for sleep apnea (17.9). Subjects with a diabetic retinopathy diagnosis had the highest number of concomitant diagnoses (mean: 6.8). Discussion: All of the diseases within the Healthy People 2010 list are purported to have at least some genetic component, with the exception of injuries. The PMRP cohort is large enough that diseases of public health importance can be studied in the context of a variety of clinical and environmental covariates. This database is being developed as a national resource and is particularly useful where the estimated disease prevalence is 5% or greater. For less common diseases, additional cases can be recruited from throughout the Marshfield Clinic system of care, with population-based controls selected from the main PMRP study cohort.