Antihypertensive drugs have been linked to new-onset diabetes (NOD); however, data on the effect of these drugs on the development of NOD in hypertensive patients has not been well determined. We aimed to investigate the association between antihypertensive drugs and NOD. This was a retrospective cohort study performed using data from claim forms provided to the central region branch of the Bureau of National Health Insurance in Taiwan from January 2002 to December 2007. Prescriptions for antihypertensive drugs before the index date were retrieved from a prescription database. We estimated the odds ratios (ORs) of NOD associated with antihypertensive drug use; nondiabetic subjects served as the reference group. A total of 4233 NOD cases were identified in 24,688 hypertensive patients during the study period. The risk of NOD after adjusting for sex and age was higher among users of diuretics (OR = 1.10, 95% confidence interval [CI]= 1.01-1.20), beta-blockers (BBS; OR = 1.12, 95% CI = 1.04-1.21), and calcium channel blockers (CCBs; OR = 1.10, 95% CI = 1.02-1.18) than among nonusers. Patients who take angiotensin-converting enzyme (ACE) inhibitors (OR = 0.92, 95% CI = 0.84-1.00), angiotensin receptor blockers (ARB; OR = 0.90, 95% CI = 0.81-0.98), or alpha-blockers (OR = 0.88, 95% CI = 0.80-0.98) are at a lower risk of developing NOD than nonusers. Vasodilators were not associated with the risk of NOD. The results of this study suggest that hypertensive patients who take ACE inhibitors, ARBs, or alpha-blockers are at a lower risk of NOD. Diuretics, BBs, and CCBs were associated with a significant increase in the risk of NOD.