Purpose Traditional blood flow restriction resistance training (BFR-Trad) is a cost-effective and time-efficient exercise modality that offers significant skeletal muscle benefits, including strength and mass gains. Despite employing low loads, BFR-Trad may not be well tolerated by all populations due to its high intensity, pain-associated muscle discomfort, low affectivity, and cardiovascular responses. Consequently, reducing BFR intensity may be an interesting approach to making traditional BFR more clinically applicable. This was approached through the proposal of the present Clinical BFR. Methods Twenty-two healthy, untrained subjects (both female and male) aged between 18 and 30 years participated. Subjects completed three sessions of unilateral knee extension exercises randomly assigned to the BFR-Trad, BFR-Clinical_c (cadenced), and BFR-Clinical_a (-autoregulated) exercise protocols. Results The BFR-Trad condition induced greater increases in perceived exertion, discomfort, delayed onset muscle soreness (DOMS), and lactate levels compared to the BFR-Clinical conditions ( p < 0.05). Muscle concentric velocity showed greater increases in the BFR-Clinical_a condition ( p < 0.001), along with higher affectivity ratings for the exercise compared to the BFR-Clinical_c and BFR-Trad conditions ( p < 0.05). Conclusion Compared to traditional BFR, clinical BFR was scored as less intense, reduced pain-associated discomfort, decreased DOMS, increased affectivity, diminished systolic blood pressure responses, decreased fatigue and muscle activation, and promoted similar glycemic responses. Altogether, our results support the potential use of clinical BFR in clinical settings.