Deep vein thrombosis (DVT) has become a severe disease with a rising incidence rate. The conventional diagnosis relies on complicated imaging modalities that may also involve invasive contrast agent injection and ionizing procedures (e.g., venography). Noninvasive near-infrared spectroscopy (NIRS) methods have been explored which required the DVT patients to follow some exercise protocols. Here, we attempt to use portable NIRS under patients’ natural state for DVT diagnosis. Nine DVT patients and seven healthy subjects participated in NIRS measurements of concentration of oxy- and deoxy-hemoglobins ( and ) relative to data on a tissue mimicking phantom at six particular sites of calves. It was found that is significantly lower in DVT patients than healthy ones, whereas is distinctly higher. Moreover, after thrombolytic therapy, both and in DVT calves assume a gradual convergence to the curves of healthy ones. This reveals the potential of NIRS for the noninvasive, continuous, and straightforward monitoring/therapeutic effect evaluation of DVT in clinics with appropriate bedside monitoring capability.