Complex regional pain syndrome type I (CRPS-I) highly affects patients' ability to perform daily life activities. Pain-related fear might be a key target to reduce disability in chronic pain. Current treatments aiming at reducing pain show little improvements on pain and disability, whereas novel exposure-based treatments targeting pain-related fears have shown to be promising. We conducted a randomized controlled trial (n = 46) comparing exposure in vivo (EXP) with pain-contingent treatment as usual (TAU), for CRPS-I patients with at least moderate levels of pain-related fear. Primary outcome is self-reported disability, for upper and lower extremity, respectively. Secondary outcomes are self-reported pain-intensity, pain-catastrophizing, perceived harmfulness of physical activity, and health-related quality of life. Pretreatment to posttreatment and pretreatment to 6-month follow-up change scores were tested using randomization-based inference. EXP was superior to TAU in reducing upper extremity disability from pretreatment to posttreatment (between-group difference 1.082; 95% confidence interval (CI) 0.563 to 1.601; p < 0.001) and from pretreatment to 6-month follow-up (1.303; 95% CI 0.917 to 1.690; p < 0.001). EXP was superior in reducing lower extremity disability from pretreatment to 6-month follow-up (3.624; 95% CI 0.467 to 6.781; p = 0.02), but not from pretreatment to posttreatment (3.055; 95% CI 20.018 to 6.128; p = 0.054). All secondary outcomes significantly favored EXP pretreatment to posttreatment, as well as pretreatment to 6-month follow-up. Exposure to daily activities shows to be more effective than a protective pain-contingent TAU in reducing self-reported disability in daily life of CRPS-I patients with at least moderate levels of pain-related fear.

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