© 2017 American Heart Association, Inc. Antihypertensive medication and low systolic blood pressure (BP) and diastolic BP have been associated with an increased falls risk in some studies. Many older adults have indicators of frailty, which may increase their risk for falls. We contrasted the association of systolic BP, diastolic BP, number of antihypertensive medication classes taken, and indicators of frailty with risk for serious fall injuries among 5236 REGARDS study (Reasons for Geographic and Racial Difference in Stroke) participants ≥65 years taking antihypertensive medication at baseline with Medicare fee-for-service coverage. Systolic BP and diastolic BP were measured, and antihypertensive medication classes being taken assessed through a pill bottle review during a study visit. Indicators of frailty included low body mass index, cognitive impairment, depressive symptoms, exhaustion, impaired mobility, and history of falls. Serious fall injuries were defined as fall-related fractures, brain injuries, or joint dislocations using Medicare claims through December 31, 2014. Over a median of 6.4 years, 802 (15.3%) participants had a serious fall injury. The multivariable-adjusted hazard ratio for a serious fall injury among participants with 1, 2, or ≥3 indicators of frailty versus no frailty indicators was 1.18 (95% confidence interval, 0.99-1.40), 1.49 (95% confidence interval, 1.19-1.87), and 2.04 (95% confidence interval, 1.56-2.67), respectively. Systolic BP, diastolic BP, and number of antihypertensive medication classes being taken at baseline were not associated with risk for serious fall injuries after multivariable adjustment. In conclusion, indicators of frailty, but not BP or number of antihypertensive medication classes, were associated with increased risk for serious fall injuries among older adults taking antihypertensive medication.