We describe a study of long-term hypertension outcomes that compares home BP telemonitoring and pharmacist case management vs. usual care. HyperLink is a cluster-randomized trial (N=450 patients) being conducted in 16 clinics of an integrated health system in Minneapolis/St. Paul, that were randomly assigned to either the Telemonitoring Intervention (TI) or Usual Care (UC). Recruitment materials are mailed to adult primary care patients whose last two BP measurements in the electronic medical record were uncontrolled in the previous 12 months. To be eligible, they are required to have uncontrolled BP confirmed at a research clinic visit. Other medical exclusion criteria are minimal: pregnancy, recent cardiovascular events, symptomatic heart failure, stage 4/5 kidney disease, and dementia. Patients in the TI arm receive a home BP telemonitor that stores and transmits BP measurements. They work with a clinical pharmacist who may adjust their treatment based on home BP according to an approved protocol. Following one intake clinic visit, participants and pharmacists communicate by telephone every 2 to 4 weeks for 6 months. Patients are instructed to take 2 to 3 BP readings on three mornings and three evenings each week, and to transmit the stored BP data to the pharmacist weekly. Adherence is defined as sending 6 home BP measurements per week. The primary outcome is BP control measured at the research clinic visit at 6 months. Secondary outcomes are BP control maintenance at 12 and 18 months, satisfaction and costs. Recruitment began March 1, 2009, and will be completed as predicted in September 2010. During the first 8 months, 195 participants were recruited, of whom 47% were female, 19% were minority race/ethnicity and 53% were from TI clinics. Adherence with the telephone visits was excellent with completion of 359/370 (97%; 95% CI 95%–99%) protocol-mandated telephone visits. Adherence to the home BP measurement schedule was also high, with 73/80 (91%; 95% CI 85%–97%) participants sending an average of 6 BP measurements per week. This novel intervention could be implemented widely in diverse and large patient populations based on performance in this randomized trial.