This prospective study was instituted to assess whether the use of the on-pump method or the off-pump method affects changes in health-related quality of life (QOL) as evaluated a year after coronary artery bypass graft (CABG) surgery. Data including preoperative risk factors and postoperative morbidity up to discharge were collected from 508 CABG patients operated in the Heart Center of a university hospital and further treated in secondary referral hospitals. Four hundred and fifty-two (89.0%) patients underwent operation with the on-pump method and 56 (11.0%) with the off-pump method, i.e., without cardiopulmonary bypass (CPB). The RAND-36 Health Survey (RAND-36) was used as indicator of QOL. The primary outcome measure was a change in the physical component summary (PCS) and mental component summary (MCS) from the RAND-36. Symptomatic status was estimated according to New York Heart Association (NYHA) class. Assessments were made preoperatively and repeated 12 months later. The majority of patients operated on-pump (85.6%) and off-pump (92.9%) had a favorable outcome without major complications (p = 0.136). The present data showed significant improvement (p < 0.001) in all eight domains of QOL following on-pump CABG. Likewise, off-pump patients improved in all eight aspects, and the change was statistically significant in six dimensions. A highly significant (p < 0.001) pattern of change was seen in the RAND-36 MCS and PCS scores in both operative groups. Differences between the groups were nonsignificant. We conclude that most patients experience significant improvement in health-related QOL during the first year after CABG, and that cardiopulmonary bypass has no effect on patients' subsequent health-related QOL, but its use depends on specific indications.