Background: Compassion fatigue is recognized as impacting the health and effectiveness of healthcare providers, and consequently, patient care. Compassion fatigue is distinct from “burnout.” Reliable measurement tools, such as the Professional Quality of Life scale, have been developed to measure the prevalence, and predict risk of compassion fatigue. This study reviews the prevalence of compassion fatigue among healthcare practitioners, and relationships to demographic variables. Methods: A systematic review was conducted using key words in MEDLINE, PubMed, and Ovid databases. Data were extracted from a total of 71 articles meeting inclusion criteria, from studies measuring compassion fatigue in healthcare providers using a validated instrument. Quantitative and qualitative data were extracted and compiled by three independent reviewers into an evidence table that included basic study characteristics, study strength and quality determination, measurements of compassion fatigue, and general findings. Meta-analysis, where data allowed, was stratified by Professional Quality of Life version, heterogeneity was quantified, and pooled means were reported with 95% confidence interval. A table of major study characteristics and results was created. Ethical consideration: This paper contains no primary data obtained directly from research participants. Data obtained from previously published resources have been acknowledged within references. Psychological distress, particularly compassion fatigue, can be insidious, no health profession is immune, and may significantly impact the ability to provide care. Results: A total of 71 studies were included. Compassion fatigue was reported across all practitioner groups studied. Relationships to most demographic variables such as years of experience and specialty were either not statistically significant or unclear. Variability in reporting of Professional Quality of Life results was found. Interpretation: Compassion fatigue exists across diverse practitioner groups. Prevalence is highly variable, and its relationship with demographic, personal, and/or professional variables is inconsistent. Questions are raised about how to mitigate compassion fatigue.