OBJECTIVES: Generic comorbidity measures developed to predict mortality and/or healthcare costs are often used as adjustment covariates in observational studies comparing health expenditures between different therapeutic strategies. The objective of this review is to identify available measures, and assess their performance for prediction of economic outcomes using large longitudinal patient databases. METHODS: We conducted a comprehensive literature search in MEDLINE, until April 2015. All methodological papers describing a new comorbidity measure or assessing their ability to predict economic outcomes using administrative data or electronic medical records were selected. We search for additional studies through references lists of selected articles. We extracted information on the conditions for using each index and predictive performance. RESULTS: