Objective: Cognitive flexibility has been previously described as the ability to adjust cognitive and behavioral strategies in response to changing contextual demands. Cognitive flexibility is typically assessed via self-report questionnaires and performance on neuropsychological tests in research and clinical practice. A common assumption among researchers and clinicians is that self-report and neuropsychological tests of cognitive flexibility assess the same or similar constructs, but the extent of the relationship between these two assessment approaches in clinical cohorts remains unknown. We undertook a systematic review and meta-analysis to determine the relationship between self-report and neuropsychological tests of cognitive flexibility in clinical samples. Method: We searched 10 databases and relevant gray literature (e.g., other databases and pearling) from inception to October 2020 and used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines. Eleven articles including 405 participants satisfied our eligibility criteria. Results: A multilevel random-effects meta-analysis revealed no relationship between self-report and neuropsychological tests of cognitive flexibility (0.01, 95% CI [−0.16 to 0.18]). Individual random-effects meta-analyses between 12 different tests pairs also found no relationship. Conclusion: Based on our results, it is clear that the two assessment approaches of cognitive flexibility provide independent information—they do not assess the same construct. These findings have important ramifications for future research and clinical practice—there is a need to reconsider what constructs self-report and neuropsychological tests of “cognitive flexibility” actually assess, and avoid the interchangeable use of these assessments in clinical samples. (PsycInfo Database Record (c) 2022 APA, all rights reserved)