BACKGROUND: the control of cardiovascular responses during resistance exercise (RE) is important for patient safety. OBJECTIVE: to investigate the influence of repetition maximum (RM) and rest interval between sets (RI) on heart rate (HR), systolic blood pressure (SBP) and rate-pressure product (RPP) during RE. METHODS: twenty healthy subjects (26 ± 5 years of age) underwent RE protocols involving three sets of leg press (6 and 12 RM) and RI proportional to the contraction time (1:3 and 1:5). The HR was checked on a continuous basis by using a cardiotachometer and the SBP was checked at the end of the sets, via a protocol validated by the auscultatory method. RESULTS: the HR was influenced by the workload (p = 0.008) and sets (p < 0.001), but not by the RI (p = 0.087). The SBP suffered from the isolated effect of the number of sets (p < 0.001) and RI (p = 0.017), but not from the workload (p = 0.95). The RPP rose in direct proportion to the workload (p = 0.036) and sets (p < 0.001), but in inverse proportion to the RI (p = 0.006). In 6 RM protocols, the variation in the HR was higher for RI = 1:3 (Δ = 11.2 ± 1.1 bpm) than for RI = 1:5 (Δ = 4.5 ± 0.2 bpm; p = 0.002), but there was no difference for 12 RM (Δ 1:3 = 21.1 ± 2.2 bpm; Δ 1:5 = 18.9 ± 2.0 bpm, p = 0.83). The RI influenced the variation in SBP in all loads (6 RM - Δ 1:3 = 10.6 ± 0.9 mmHg, Δ 1:5 = 6.6 ± 0.7 mmHg; p = 0.02 and 12 RM - Δ 1:3 = 15.2 ± 1.1 mmHg, Δ 1:5 = 8.4 ± 0.7 mmHg; p = 0.04). The RPP rose in proportion to the workload (p = 0.036) and to the sets (p < 0.001), but in inverse proportion to the RI (p = 0.006). With RI = 1:3, there was difference in RPP for 6 RM (Δ = 2,892 ± 189 mmHg.bpm) and 12 RM (Δ = 4,587 ± 300 mmHg.bpm; p = 0.018), but not with RI = 1:5 (6 RM: Δ = 1,224 ± 141 mmHg.bpm, 12 RM: Δ = 2,332 ± 194 mmHg.bpm; p = 0.58). CONCLUSION: regardless of the workload, an increased RI was associated with lower cardiovascular responses during RE, especially of SBP.