It has often been postulated that simple, short questionnaires are unable to reflect complex changes in well-being of individuals with chronic psychiatric disorders. To investigate these assumptions we included two recently developed instruments to measure quality of life (the WHOQoL-Bref and the EuroQoL EQ-5D) in a randomised control trial (RCT) in which two treatment conditions were compared. Aims of the study were to assess the sensitivity and validity of these quality of life (QoL)-instruments, to establish their relationship and to examine the predictors of changes in QoL. Subjective changes in QoL were measured on three assessments waves in a period of 18 months and compared to objective changes in psychopathology and social functioning in a sample of 76 chronic schizophrenic patients who participated in the RCT. Results indicated that both WHOQoL-Bref and EuroQoL EQ-5D are capable of detecting changes in QoL over time in physical and psychological well-being. The instruments partly measure the same aspects of QoL, indicated by 50% common variance on total scores. Reduction of positive psychotic symptoms appeared to be the most important factor in improving QoL. The weighted TTO-score of EuroQoL-5D, which is often used as an index in economic evaluations of health care, did however not correspond with these changes, which indicates that it is less sensitive to changes in social and psychological well-being. It's use as the core measure in (economic) health evaluation in the field of psychiatry therefore seems less appropriate.