Initial evidence suggested that people with Complex Regional Pain Syndrome (CRPS) have reduced attention to the affected side of their body and the surrounding space, which might be related to pain and other clinical symptoms. Three previous unblinded, uncontrolled studies showed pain relief following treatment with prism adaptation, an intervention that has been used to counter lateralised attention bias in brain-lesioned patients. To provide a robust test of its effectiveness for CRPS, we conducted a double-blind randomized controlled trial of prism adaptation for unilateral upper-limb CRPS-I. Forty-nine eligible adults with CRPS were randomized to undergo two-weeks of twice-daily home-based prism adaptation treatment (n = 23) or sham treatment (n = 26). Outcomes were assessed in person four weeks prior to and immediately before treatment, and immediately after and four weeks post-treatment. Long-term postal follow-ups were conducted three and six months after treatment. We examined the effects of prism adaptation versus sham treatment on current pain intensity and CRPS symptom severity score (primary outcomes); as well as sensory, motor, and autonomic functions, self-reported psychological functioning, and experimentally tested neuropsychological functions (secondary outcomes). We found no evidence that primary or secondary outcomes differed between the prism adaptation and sham treatment groups when tested at either time point following treatment. Overall, CRPS severity significantly decreased over time for both groups, but we found no benefits of prism adaptation beyond sham treatment. Our findings do not support the efficacy of prism adaptation treatment for relieving upper-limb CRPS-I. This trial was prospectively registered (ISRCTN46828292).