The purpose of this systematic literature review was to identify clinical trials of MDS and AML that included patient-reported outcome (PRO) instruments, and to summarize the symptom and other health related quality of life (HRQOL) concepts most frequently assessed and the PRO instruments that were used. Sixteen manuscripts describing 14 distinct trials met all criteria (i.e., phase 2 or 3 clinical trial for MDS or AML which included PRO assessment) and were published between 1996-2017. In trials evaluating anemia, PRO scores showed significant improvement in relevant domains (e.g. fatigue, function) among patients identified as responders. In trials evaluating the impact of anti-cancer therapies, improvements the baseline to end of treatment were observed in physical functioning and HRQOL, however the rates of missing data in many of the trials was high or unreported. PRO instruments have the ability to capture changes over time in patients' function and well-being, and PRO instruments and guidance documents are available to support the assessment of HRQOL in AML/MDS clinical trials.