Monitoring national patterns of antihypertensive drug therapy is essential to assessing adherence to treatment guidelines and the impact of major scientific publications on physician prescribing. We analyzed data from 2 US National Ambulatory Care Surveys to examine trends between 1993 and 2004 in the prescription of antihypertensive drug classes for uncomplicated hypertension and the association between thiazide and beta-blocker prescribing and physician and patient characteristics. Diuretic prescriptions remained level through 2001 (39%; 95% CI: 34% to 44%) but increased to 53% (48% to 58%) in 2003, largely because of a 72% increase in thiazide prescriptions in the first quarter of 2003 (50%; 95% CI: 40% to 59%). However, these increases did not sustain in 2004. Beta-blocker prescriptions increased modestly from 1993 (24%; 95% CI: 19% to 29%) to 2004 (33%; 95% CI: 28% to 39%). Prescription of calcium channel blockers and angiotensin-converting enzyme inhibitors declined significantly following the sixth Joint National Committee report, but both subsequently rebounded to prereport levels. Prescription of angiotensin II receptor blockers increased continuously from 1% in 1995 to 23% by 2004. Polytherapy prescriptions, particularly those involving > or = 3 drug classes, became increasingly prevalent, accounting for 60% of antihypertensive drug visits by 2004. Prescriptions of thiazides and beta-blockers were both more likely in 1998-2004 (versus 1993-1997). Blacks, women, and hospital outpatients were more likely to receive thiazides. Also, cardiologists were more likely to prescribe beta-blockers. Evidence-based guidelines for antihypertensive drug therapy do impact physician prescribing, but the impact seems to be short lived. Future interventions are imperative for promoting long-term adherence to published guidelines.