Hammert, WB, Moreno, EN, Martin, CC, Jessee, MB, and Buckner, SL. Skeletal muscle adaptations to high-load resistance training with pre-exercise blood flow restriction. J Strength Cond Res 37(12): 2381-2388, 2023-This study aimed to determine if blood flow restriction (BFR) could augment adaptations to a high-load training protocol that was inadequate for muscle growth. Forty nontrained individuals had each arm assigned to 1 of 3 elbow flexion protocols: (a) high-load resistance training [TRAD; 4 sets to muscular failure at 70% 1 repetition maximum (1RM)], (b) low repetition high-load resistance training with pre-exercise BFR (PreBFR; 4 sets of 3 repetitions at 70% 1RM + 3 min of pre-exercise BFR), and (c) low repetition high-load resistance training (LRTRAD); 4 sets of 3 repetitions at 70% 1RM). Muscle thickness (MT), 1RM strength, and local muscular endurance (LME) of the elbow flexors were measured before and after 8 weeks. An alpha level of 0.05 was used for all comparisons. For the 50% site, MT increased for TRAD (0.211 cm, 95% confidence interval [95% CI]: 0.143-0.280), PreBFR (0.105 cm, 95% CI: 0.034-0.175), and LRTRAD (0.073 cm, 95% CI: 0.000-0.146). The change for TRAD was greater than PreBFR and LRTRAD. For the 60% site, MT increased for TRAD (0.235 cm, 95% CI: 0.153-0.317), PreBFR (0.097 cm, 95% CI: 0.014-0.180), and LRTRAD (0.082 cm, 95% CI: 0.000-0.164). The change for TRAD was greater than PreBFR and LRTRAD. For the 70% site MT increased for TRAD (0.308 cm, 95% CI: 0.247-0.369), PreBFR (0.103 cm, 95% CI: 0.041-0.166), and LRTRAD (0.070 cm, 95% CI: 0.004-0.137). The change for TRAD was greater than PreBFR and LRTRAD. One repetition maximum and LME significantly increased for each condition, with no differences between conditions. Collapsed across conditions 1RM strength increased 2.094 kg (95% CI: 1.771-2.416) and LME increased 7.0 repetitions (95% CI: 5.7-8.3). In conclusion, the application of BFR to low-repetition, high-load training did not enhance the adaptative response.