© 2016 Background The association between hyperuricemia and hypertension is controversial. Animal models, epidemiological data, and small clinical trials have favored a causative role for hyperuricemia in hypertension but more studies are necessary to elucidate putative mechanisms, population susceptibility, and potential for urate-lowering therapies (ULT) to decrease blood pressure (BP). Purpose To describe the background and design of the Serum Urate Reduction to Prevent Hypertension (SURPHER) study. Methods SURPHER is a single center, double-blinded, crossover trial in which participants are randomly assigned to allopurinol (300 mg) or placebo. Enrollment focused on adults 18–40 years old with baseline systolic blood pressure ≥ 120 and < 160 mm Hg or diastolic blood pressure ≥ 80 and < 100 mm Hg, and serum urate ≥ 5.0 mg/dL or ≥ 4.0 mg/dL for men or women, respectively. SURPHER recruitment targets participants without chronic kidney disease (estimated glomerular filtration rate > 60 mL/min/1.73 m2), and without prior diagnosis of gout or use of ULT to treat gout. The primary outcome is change from baseline in blood pressure assessed by 24 hour ambulatory blood pressure monitoring and mechanistic outcomes include changes in endothelial function as measured by flow-mediated dilation, as well as C-reactive protein levels. Results Since June 16, 2014 until present, SURPHER is recruiting participants in the city of Birmingham, Alabama. Limitations The study aims to enroll otherwise healthy young adults for a pharmacological intervention study with multiple study-related procedures. Challenges related to recruitment are anticipated and multiple strategies for increasing recruitment and retention are planned if necessary.