OBJECTIVES: The role of ‘disinvestment’ in health care, i.e., the withdrawal (partially or completely) of interventions that provide no or marginal benefit compared to alternative therapeutic approaches is attracting worldwide attention.  The objective of this study was to identify and review empirical evaluations of disinvestment programs to gauge their success and determine key challenges. METHODS: We systematically searched the medical literature using the PubMed database for empirical evaluations of disinvestment programs using the following search terms; “disinvestment”, “resource allocation”, “low value”, and “priority setting”.  We did not restrict our search in regards to study publication year. Two researchers assessed each identified abstract.  For each study, we reported the disinvestment program that was assessed and categorized study findings as ‘successful’ if a reduction in utilization of the low-value service was reported, and ‘unsuccessful’ if no reduction in utilization was reported.  We also reported challenges identified by the study authors in the implementation of the disinvestment program. RESULTS: We identified 34 studies describing empirical evaluations of disinvestment programs.  Fifteen pertained to the National Institute for Health and Care Excellence’s recommendations, and/or their ‘do not do list,’ 8 pertained to the Choosing Wisely Campaign,  and 11 pertained to unique initiatives worldwide—including the French initiative to delist unnecessary pharmaceuticals with the help of its Transparency Commission. The empirical evaluations varied with respect to the reported success of the disinvestment programs:  twenty-one determined the program to be successful, and 13 unsuccessful.  Common challenges reported by study authors include difficulty in identifying low-value care for disinvestment and gaining support among stakeholders. CONCLUSIONS: Empirical evaluation of disinvestment programs is limited. Available evaluations report varied success for existing disinvestment strategies and noted that a number of key challenges are yet to be overcome.