This study examined themes relevant to health-related quality of life as identified by patients undergoing major surgery and by health care providers. Semi-structured interviews were conducted with 52 patients undergoing major abdominal, cardiac, orthopedic, thoracic, or vascular surgical procedures and 33 health professionals from various disciplines. A total of 58 themes were identified by content analysis. These themes were categorized into 6 domains. These were: physical well-being (14 themes), emotional well-being (13 themes), concern about quality of care (12 themes), social well-being (12 themes), cognitive preparation (4 themes), and spiritual well-being (3 themes). In general, we found that most aspects of health-related quality of life were common across various major surgical procedures and between patients and health care providers. However, when we examined the coverage of these themes in seven commonly-used health-related quality of life instruments, we found that many of the most frequently mentioned themes were not assessed with the available measures. A new evaluative instrument tailored to patients undergoing major surgery may therefore be warranted.