OBJECTIVES: Systolic heart failure (HF), is a progressive condition carrying a high risk of mortality, hospitalisation and having a significant detrimental impact on quality of life (QoL). Current therapies indicated for use in this patient population demonstrated beneficial effects on QoL, however the magnitude of effects remain debatable. This review was performed to identify QoL instruments (disease specific and generic) used in systolic heart failure, to estimate the impact of various pharmacological interventions. METHODS: Publications resulting from Randomised controlled trials (RCTs) as well as post-hoc analysis of RCTs from 1996 to October 21, 2014 were selected using pre-defined inclusion criteria. Critical appraisal of trials was performed using the NICE risk of bias tool. RESULTS: A total of 37 publications from 33 RCTs met the inclusion criteria. The main HF-specific QoL instruments used were the Minnesota Living with Heart Failure Questionnaire (MLHFQ) (8,004 patients) in 19 trials and the more recent Kansas City Cardiomyopathy Questionnaire (KCCQ) (12,101 patients) in four trials. The generic EQ-5D (VAS) was used in three trials whereas SF-36 was used in two trials. Four studies also reported correlations between end point changes in morbidity or mortality and change in QoL. Significant changes in QoL were found in 9 active and 5 placebo-controlled trials respectively, which could be attributed to various pharmacological interventions. The critical appraisal concluded that the studies were of moderate quality.  CONCLUSIONS: The majority of included RCTs used HF-specific questionnaires, to measure QoL. From 2009 onwards, the use of KCCQ increased compared to MLHFQ and KCCQ was administered to a comparatively larger study population. Thus, QoL data retrieved from studies using KCCQ are considered to be more representative of the real world.  The inconsistency in reporting of QoL results in RCTs limited comparison of the treatment impact on QoL