Stress BOLD MRI allows for quantitative evaluation of blood flow reserve in skeletal muscles. In this study, we conducted a head-to-head comparison between three commonly used stressors including gas inhalation, cuff compression induced ischemia and postocclusive reactive hyperemia, and exercise. Results showed that different paradigms could produce different BOLD signal variation profiles. Both correlation and discrepancy can be noted regarding to the relationship between BOLD MRI and TcPO2 measurements. Ischemia and reactive hyperemia paradigm had better interobserver/interscan reproducibility, exercise had larger signal alterations, and both can reveal the age-dependent differences in BOLD signal and may be preferred in further applications.