Background: Complex Regional Pain Syndrome (CRPS) presents as chronic, continuous pain and sensory, autonomic, and motor abnormalities affecting one or more extremities. People with CRPS can also show changes in their perception of and attention to the affected body part and sensory information in the affected side of space. Prism Adaptation (PA) is a behavioural intervention targeted at reducing attention deficits in post-stroke hemispatial neglect. PA also appears to reduce pain and other CRPS symptoms; however, these therapeutic effects have been demonstrated only in small unblinded studies. This paper describes the protocol for an ongoing double-blind, randomized, sham-controlled clinical trial that will evaluate the efficacy of PA treatment for CRPS. The secondary aims of the study are to examine the relationships between neuropsychological changes (such as spatial attention, space and body representation, and motor spatial performance) and clinical manifestations of CRPS, as well as symptom improvement. Methods: Forty-two participants with upper-limb CRPS type I will undergo two weeks of twice-daily PA treatment or sham treatment. The primary outcome measures are current pain intensity and CRPS severity score, measured immediately before and after the treatment period. Secondary outcome measures include the results of self-report questionnaires about pain, movement, symptoms interference, and body representation; clinical assessments of sensory, motor, and autonomic functions; and computer-based psychophysical tests of neuropsychological functions. Data are collected in four research visits: four weeks and one day before treatment, and one day and four weeks after the end of treatment. Additional follow-up through postal questionnaires is conducted three and six months post-treatment. Discussion: It is hypothesised that participants undergoing PA treatment, compared to those receiving sham treatment, will show greater reduction in pain and CRPS severity score, and improvements on other clinical and neuropsychological measures. Also, more pronounced neuropsychological symptoms are predicted to correlate with more severe clinical CRPS symptoms. This study will provide the first randomized double-blind evaluation of the therapeutic effects of PA that could be implemented as a rehabilitation method for CRPS, and will contribute to the understanding of how neuropsychological changes in body representation and attention pertain to the manifestation and treatment of CRPS.