Despite the established role of compression as the basis for nonoperative treatment of chronic venous insufficiency (CVI), its mechanism of action remains unclear. Near-infrared spectroscopy (NIRS) provides continuous noninvasive monitoring of changes in tissue oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb). We applied NIRS to evaluate the effect of graded stockings on venous function and calf muscle oxygenation during exercise in patients with CVI. Ten patients (age 56 +/- 5 years) with CVI were rested in supine posture for 20 minutes. NIRS optodes were attached to the calf. Venous function was assessed in each patient with and without graded compression stockings (classes I to III) at rest in the supine position, standing, with 10 tiptoe exercises, and on standard walking at 1.6 km/h for 5 minutes. Venous function was assessed by measuring changes in Hb and total hemoglobin (HbT) during the test, and muscle oxygenation was assessed by the oxygenation index (HbD), which is the difference between HbO2 and Hb. Standing without stockings caused a significant increase in Hb concentration by 10.75 +/- 2.24 micromol/L compared with the supine position (p < .001). This value was reduced when stockings were applied to 6.38 +/- 2.75 micromol/L with class III stockings (p = .005). During tiptoe exercise, the residual Hb concentration value without stockings was 7.62 +/- 2.12 micromol/L compared with 5.88 +/- 2.87, 3.77 +/- 3.37, and 3.46 +/- 2.73 micromol/L for class I, II, and III stockings, respectively. The reduction in Hb concentration reached significance with class II and III stockings compared to without stockings (p = .04). The HbT concentration was also reduced during tiptoe exercise, with increasing compression from 15.46 +/- 5.31 micromol/L without compression to 11.52 +/- 4.26 pmol/L with class III stockings (p = .048). During walking, the Hb concentration was 11.40 +/- 3.10 pmol/L without stockings, decreasing significantly (p < .001) and progressively to 8.49 +/- 3.24, 7.71 +/- 3.51, and 6.89 +/- 3.16 micromol/L with class I, II, and III stockings, respectively. Limb oxygenation (as measured by HbO2 concentration) during walking exercise, however, increased with higher-compression stockings and reached significance with class III stockings only (p = .03). In patients with venous insufficiency, graduated compression stockings may achieve their beneficial effects by reducing venous pooling and improving deeper tissue oxygenation.