PurposeQuality of life (QOL) is an important concept in the field of health and medicine. QOL is a complex concept that is interpreted and defined differently within and between disciplines, including the fields of health and medicine. The aims of this study were to systematically review the literature on QOL in medicine and health research and to describe the country of origin, target groups, instruments, design, and conceptual issues.MethodsA systematic review was conducted to identify research studies on QOL and health-related quality of life (HRQOL). The databases Scopus, which includes Embase and MEDLINE, CINAHL, and PsycINFO were searched for articles published during one random week in November 2016. The ten predefined criteria of Gill and Feinstein were used to evaluate the conceptual and methodological rigor.ResultsQOL research is international and involves a variety of target groups, research designs, and QOL measures. According to the criteria of Gill and Feinstein, the results show that only 13% provided a definition of QOL, 6% distinguished QOL from HRQOL. The most frequently fulfilled criteria were: (i) stating the domains of QOL to be measured; (ii) giving a reason for choosing the instruments used; and (iii) aggregating the results from multiple items.ConclusionQOL is an important endpoint in medical and health research, and QOL research involves a variety of patient groups and different research designs. Based on the current evaluation of the methodological and conceptual clarity of QOL research, we conclude that the majority QOL studies in health and medicine have conceptual and methodological challenges.Electronic supplementary materialThe online version of this article (doi:10.1007/s11136-019-02214-9) contains supplementary material, which is available to authorized users.