Purpose: The aim of this systematic review was to evaluate the effect of immersive and non-immersive interactive virtual reality on pain perception in patients with a clinical pain condition.Methods: The following databases were searched from inception: Medline (Ovid), PsychInfo, CINAHL, Cochrane library and Web of Science. Two reviewers screened reports and extracted the data. A third reviewer acted as an arbiter. Studies were eligible if they were randomized controlled trials, quasi-randomized trials, and uncontrolled trials. Crossover and parallel-group designs were included. Risk of bias was assessed for all included studies.Results: Thirteen clinical studies were included. The majority of studies investigated a sample of participants with chronic pain. Six were controlled trials and seven uncontrolled studies. Findings from controlled research suggest that interactive virtual reality may reduce pain associated with ankylosing spondylitis and post-mastectomy, but results are inconsistent for patients with neck pain. Findings from uncontrolled studies suggest that interactive virtual reality may reduce neuropathic limb pain, and phantom limb pain, but had no effect on nonspecific chronic back pain.Conclusions: There is a need for more rigorous randomized control trials in order to conclude on the effectiveness of the use of virtual reality for the management of pain.Implications for rehabilitationInteractive virtual reality has been increasingly used in the rehabilitation of painful conditions.Interactive virtual reality using exergames may promote distraction from painful exercises and reduce pain post-mastectomy and in patients with ankylosing spondylitis.Interactive virtual representation of limbs may reduce neuropathic and phantom limb pain.