Exercise with blood flow restriction promotes significant improvements, and it has been considered an attractive exercise strategy, especially for older individuals. However, the acute cardiovascular responses to resistance exercise with blood flow restriction (BFR) are not fully known. The purpose of this study was to evaluate the hemodynamic responses during resistance exercise with BFR in young and older individuals. We compared hemodynamic responses in 15 young (30 ± 3 years) and 12 older (66 ± 7 years) subjects during low-intensity resistance biceps curl exercise with (BFR-RE) or without (RE) BFR in a random and crossover design. Heart rate (HR), mean blood pressure (MBP), calf blood flow (CBF), and calf vascular resistance (CVR) were evaluated. Both groups presented similar values at baseline. Compared with RE, HR and MBP were higher during BFR-RE for both the groups, and these changes were maintained during the recovery period. In both the groups, BFR-RE elicited larger decreases in CBF and increased CVR. Both groups showed a significant increase in double product during BFR-RE. In conclusion, resistance exercise with BFR elicits greater hemodynamic changes in healthy young and older subjects, with responses of similar magnitudes in both groups. The safety of BFR in clinical practice demands further study in vulnerable populations.