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Purpose/Objective: Acceptance and commitment therapy (ACT), a newer type of behavior therapy that targets psychological flexibility, may have particular utility in the context of muscle disorders. However, there has been no formal investigation of psychological flexibility in this population. This longitudinal observational study investigated whether psychological flexibility is cross-sectionally related to, and prospectively influential on, life satisfaction and mood in muscle disorders. Methods: Data were collected via online questionnaire batteries, completed at baseline and then repeated 4 months later. Cross-sectional and prospective regression analyses examined relationships between validated measures of disability level, psychological flexibility (experiential avoidance, cognitive fusion, and valued living) and illness perceptions (a psychological variable with known influence in muscle disorders), and outcomes (life satisfaction, anxiety, and depression). Results: A sample of 137 people with a range of muscle disorders participated. In cross-sectional analyses, psychological flexibility explained significant unique variance in addition to illness perceptions (ΔR2 = 0.17–0.34, p < .001). In prospective analyses, psychological flexibility alone was predictive of change in life satisfaction (ΔR2 = 0.04, p = .01) and anxiety (ΔR2 = 0.03, p = .04) over 4 months. No independent variables were predictive of change in depression over 4 months, and disability level had no significant influence on outcomes. Conclusions: Psychological flexibility influences important outcomes in muscle disorders. Experimental studies are required to establish if increased psychological flexibility leads to improved outcomes.