OBJECTIVES: To identify and characterise studies that have used quality-adjusted life years (QALYs) based on actual measurements of patients' health-related quality of life (HRQoL) as an indicator of effectiveness of screening programmes. METHODS: Systematic search of the literature until March 2010, using several electronic databases. Initial screening of articles was based on abstracts, and evaluation of full-text articles was done independently by at least two of the authors. The final inclusion decision was based on consensus. RESULTS: The search identified 1610 articles. The use of QALYs in evaluation of screening programmes has expanded in recent years as 617 of the articles had been published between 2007 and 2010, while the corresponding figure between 1966 and 2010 was 993. Based on review of abstracts, 431 full-text articles were obtained for closer inspection. Of the reviewed full-text articles, 78 reported QALYs based on patient-derived data using a valid HRQoL assessment. The most frequently used method was Time Trade-Off (55%) followed by Standard Gamble (21%) and  EQ-5D (26%). The most frequently studied medical conditions were malignant diseases (22%) followed by cardiovascular diseases (19%). The majority of the studies came from the USA (46%) or the UK (27%). All studies employed some kind of modelling with the Markov model being the most prevalent type (62%). Most articles (71%) concluded that the screening programme studied was cost-effective. Most of the studies included in the review were of high quality, but there were still a lot of variation as to which outcome measures were chosen, and only few studies reported incremental analysis. CONCLUSIONS: The use of QALYs in the evaluation of cost-effectiveness of screening programmes has expanded during the last few years. However, only a minority of studies have employed actual patient- derived HRQoL data.