Background: While fixed dose combinations (FDCs) of long-acting beta 2-agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) are increasingly tested on their efficacy in improving lung function, their effectiveness on Patient Reported Outcomes (PROs) such as Health Related Quality of Life (HRQoL) and Health Status (HS) deserve more attention. Objectives: To review current available evidence about the treatment effect of fixed LABA/LAMA FDCs on HRQoL. Methods: A systematic literature search for randomized controlled trials (RCTs) about the impact of LABA/LAMA FDCs versus placebo, LABA or LAMA or LABA/ICS on HRQoL in Chronic obstructive pulmonary disease (COPD) patients has been performed. Results: Twenty-eight RCTs (n = 32, 165 COPD patients) investigating the impact of fixed LABA/LAMA combinations on HRQoL were included. Using the St George’ s Respiratory Questionnaire, 27 out of 28 trials assessed HRQoL. LABA/LAMA FDCs significantly improved HRQoL versus placebo in 9 out of 11 trials, while change when compared to other LABA or LAMA monocomponents was significantly better in 11 out 24. In 5 out of 6 RCTs having LABA/ICS as comparators, LABA/LAMA FDC had a similar effect and only 1 showed significant improvement in HRQL compared to LABA/ICS FDC. Conclusion: LABA/LAMA FDCs may be helpful in improving HRQoL, but because of the heterogeneity of performed trials, strong conclusions cannot be drawn. Moreover, due to the different molecule properties, treatment schedule, and device characteristics of each FDC, a generalized judgment seems inappropriate. Pragmatic trials powered to detect real-life differences in HRQoL and head-to-head comparison are needed to guide clinical practice in terms of PROs.