BACKGROUND: We aimed to characterize the genetic architecture of resistant hypertension (rHTN), which affects up to 18% of hypertensive individuals and increases cardiovascular disease risk. METHODS: We conducted a genome-wide association study on rHTN, defined as use of 3 or more concomitant antihypertensive drugs for at least 6 months without reaching blood pressure target (in the 3-drug case), comparing it to controlled hypertension (cHTN), in which persons on 1 or 2 antihypertensives for at least 6 months reach target BP after 30 days of therapy initiation. The study included 23 508 rHTN cases and 24 393 cHTN controls, identified through drug prescription and blood pressure data from Iceland (deCODE), the UK (UK Biobank), and the US (eMERGE).