To determine the effects of load and blood flow restriction (BFR) on muscular responses, we asked 12 participants to perform chest presses under four different conditions [30/0, 30/40, 50/0, and 50/40, presented as percentage one-repetition maximum (1RM)/percentage arterial occlusion pressure (AOP)]. Muscle thickness increased pre- to post-exercise [chest: mean 0.29, 95% confidence interval (CI) 0.21, 0.37 cm; triceps: mean 0.44, 95% CI 0.34, 0.54 cm], remaining elevated for 15 min post-exercise. Electromyography amplitude was greater with 50% 1RM and increased over time for the first three repetitions of each set of chest presses. The last three repetitions differed across time only. AOP increased from pre- to post-exercise, augmented by BFR [30/0: mean 31, 95% CI 18, 44 mmHg; 30/40: mean 39, 95% CI 28, 50 mmHg; 50/0: mean 32, 95% CI 23, 41 mmHg; 50/40: mean 46, 95% CI 32, 59 mmHg). Tranquility decreased and physical exhaustion increased from the pre- to post-condition, with both parameters returning to the baseline 15 min post-exercise level. In conclusion, load and BFR do not elicit meaningful differences in the acute response of chest press exercise taken to failure.