Experiential avoidance (EA) has been conceptualized as the tendency to avoid negative internal experiences and is an important concept in numerous conceptualizations of psychopathology as well as theories of psychotherapy. Existing measures of EA have either been narrowly defined or demonstrated unsatisfactory internal consistency and/or evidence of poor discriminant validity vis-à-vis neuroticism. To help address these problems, we developed a reliable self-report questionnaire assessing a broad range of EA content that was distinguishable from higher order personality traits. An initial pool of 170 items was administered to a sample of undergraduates (N = 312) to help evaluate individual items and establish a structure via exploratory factor analyses. A revised set of items was then administered to another sample of undergraduates (N = 314) and a sample of psychiatric outpatients (N = 201). A 2nd round of item evaluation was performed, resulting in a final 62-item measure consisting of 6 subscales. Cross-validation data were gathered in 3 new, independent samples (students, N = 363; patients, N = 265; community adults, N = 215). The resulting measure (the Multidimensional Experiential Avoidance Questionnaire, or MEAQ) exhibited good internal consistency, was substantially associated with other measures of avoidance, and demonstrated greater discrimination vis-à-vis neuroticism relative to preexisting measures of EA. Furthermore, the MEAQ was broadly associated with psychopathology and quality of life, even after controlling for the effects of neuroticism.