Atherosclerosis plays an important role in saphenous vein graft disease (SVGD). Previous trials showed that inflammatory blood cells play a role in this process. The platelet to lymphocyte ratio (PLR) has been proposed as a novel predictor for cardiovascular risk and indicator of atherosclerosis. The aim of this study was to assess the relationship between SVGD and PLR. A total of 220 patients with SVG were enrolled (n = 87 with SVGD and n = 133 with patent SVG). A 50% stenosis within the SVG was defined as clinically significant. Median PLR (P < .001) and mean platelet volume (MPV; P = .043) were significantly higher in patients with SVGD. Also, PLR showed significantly positive correlation with age of SVG (P < .05). Median age of SVGs was also higher in the SVGD group (P = .025). In multivariate logistic regression analyses, the PLR and MPV were independent predictors of SVGD. Using a cutoff level of 106.3, the PLR predicted SVGD with a sensitivity of 87.4% and a specificity of 80.3%. To the best of our knowledge, this study showed, for the first time, that PLR was independently associated with SVGD. Both PLR and MPV might predict SVGD.