Antihypertensive medication and low systolic and diastolic blood pressure (SBP and DBP) 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 SBP, DBP, number of antihypertensive medication classes taken, and indicators of frailty with risk for serious fall injuries among 5,236 REasons for Geographic and Racial Difference in Stroke study participants ≥65 years taking antihypertensive medication at baseline with Medicare fee-for-service coverage. SBP and DBP 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 were 1.18 (95% confidence interval [CI], 0.99–1.40), 1.49 (95%CI, 1.19–1.87) and 2.04 (95%CI, 1.56–2.67), respectively. SBP, DBP, 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.