Resistance training with blood flow restriction (RTBFR) allows physically impaired people living with HIV (PWH) to exercise at lower intensities than traditional resistance training (TRT). But the acute and chronic cardiac and metabolic responses of PWH following an RTBFR protocol are unknown. The objective was to compare the safety of acute and chronic effects on hemodynamic and lipid profiles between TRT or RTBFR in PWH. In this randomized control trial, 14 PWH were allocated in RTBFR (GRTBFR; n = 7) or TRT (GTRT; n = 7). Both resistance training protocols had 36 sessions (12 weeks, three times per week). Protocol intensity was 30% (GRTBFR) and 80% (GTRT). Hemodynamic (heart rate, blood pressure) and lipid profile were acutely (rest and post exercise 7th, 22nd, and 35th sessions) and chronically (pre and post-program) recorded. General linear models were applied to determine group * time interaction. In the comparisons between groups, the resistance training program showed acute adaptations: hemodynamic responses were not different (p > 0.05), regardless of the assessment session; and chronicles: changes in lipidic profile favors GRTBFR, which significantly lower level of total cholesterol (p = 0.024), triglycerides (p = 0.002) and LDL (p = 0.030) compared to GTRT. RTBFR and TRT induced a similar hemodynamic adaptation in PWH, with no significant risks of increased cardiovascular stress. Additionally, RTBFR promoted better chronic adequacy of lipid profile than TRT. Therefore, RTBFR presents a safe resistance training alternative for PWH.