This investigation examined a moderate individualized pressure (i.e., percentage of total arterial occlusion pressure [TAOP]) compared to low and high absolute pressures on muscle tissue oxygenation (StO2) throughout ischemic preconditioning (IPC). Fifteen males randomly completed three cycles of IPC at a low (20 mmHg [IPCSHAM]), moderate (80% of TAOP [IPC80%]), and high (220 mmHg [IPC220mmHg]) pressure. Each cycle lasted 5 min at the assigned pressure, followed by 5 min of zero pressure on the dominant leg. StO2 was measured continuously and StO2 indices (i.e., downslope [StO2down], minimum [StO2min], upslope [StO2up], maximum [StO2max]) were analyzed with Bayesian models. StO2down and StO2min were pressure-dependent (IPCSHAM textless IPC80% textless IPC220mmHg) as indicated by zero absent from all 95% high-density intervals (95% HDI) and 100% probability of an effect (Prob = 100%). During IPC220mmHg, StO2up increased from cycle 1 to cycles 2 and 3 but plateaued from cycle 2 to 3 as indicated by zero absent from all 95% HDI’s and Prob ≥87.6%. Additionally, StO2up was greater for IPC80% and IPC220mmHg relative to IPCSHAM for cycles 1 and 2 but was pressure-dependent during cycle 3 as indicated by zero absent from all 95% HDI’s and Prob = 98.8%. Lastly, StO2max was greater for IPC220mmHg than IPCSHAM and IPC80% as indicated by zero absent from all 95% HDI’s and Prob = 100%. Collectively, using moderate individualized pressure elicited similar StO2up as high absolute pressure, but only for cycles 1 and 2. These findings may be attributed to differences in the hypoxic-insult and/or vascular-related mechano-transduction stimuli.