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Fear of (re)injury/movement has been identified as a potential predictor of chronic disability in complex regional pain syndrome type I (CRPS-I). In order to reduce pain-related fears and pain disability, graded exposure in vivo (GEXP) is likely to be an appropriate treatment. Indeed, there is evidence that in chronic pain patients reporting substantial fear of (re)injury/movement, GEXP is successful in reducing pain disability. However, the efficacy of exposure-based protocols in the treatment of CRPS-I patients for reducing pain disability has not been tested. The main research question of this study was whether the reduction of pain-related fear through GEXP also resulted in a decrease of disability in a subgroup of patients with CRPS-I who report substantial pain-related fear. A single-case experimental ABCD-design was used with random determination of the start of the intervention. Eight patients with CRPS-I were included in the study. To assess daily changes in pain intensity, pain-related fear, pain catastrophizing, and activity goal achievement, a diary was used. Standardized questionnaires of pain-related fear, pain disability, and self-reported signs and symptoms of CRPS-I were administered before and after each intervention, and at 6-month follow-up. The current study supports a GEXP approach to chronic CRPS-I. The GEXP was successful in decreasing levels of self-reported pain-related fear, pain intensity, disability, and physiological signs and symptoms. These results support the hypothesis that the meaning people attach to a noxious stimulus influences its experienced painfulness, and that GEXP activates cortical networks and reconciles motor output and sensory feedback.