Objectives: To compare health-related quality of life of patients primarily treated with a no-touch saphenous vein graft with that of patients who received a conventional graft. Methods: The study included all individuals treated with a percutaneous coronary intervention on a saphenous vein graft between January 2006 and June 2020. The RAND-36 health survey was used to assess health-related quality of life. The Mann–Whitney U test was used to test differences in health-related quality of life between the two groups. Effect size was estimated via Cohen’s d. The average treatment effect between the groups was tested by propensity score matching. Results: Of the 346 patients treated with a percutaneous coronary intervention in a stenosed or occluded saphenous vein graft, 165 responded to RAND-36 (no-touch: n=48; conventional: n=117). Patients with a no-touch graft reported better mean values on seven of the eight health survey domains. Statistically significant differences were observed for four of the domains, all in favour of the no-touch group. The effect size estimates indicated a small difference for five domains, with the largest values (>0.40) seen for the general health and energy/fatigue domains. Propensity score matching confirmed a statistically significant difference for the physical functioning and general health domains. Conclusions: At a mean follow-up of 5.4 years, patients who received a percutaneous coronary intervention in no-touch vein grafts showed significantly better health-related quality of life than those who received a percutaneous coronary intervention in conventional vein grafts.