Purpose: The aim of this systematic review was to determine the efficacy of thoracic spine manipulation (TSM) in reducing pain and disability in patients diagnosed with non-specific neck pain. Methods: An extensive literature search of PubMed, The Cochrane Library, CINAHL and EMBASE was conducted in February 2012. Randomized controlled trials (RCTs) or controlled clinical trials evaluating the effect of TSM in patients aged 18 to 65 years with non-specific neck pain were eligible. Methodological quality of the studies was assessed according to the Physiotherapy Evidence Database scale (PEDro). Qualitative analyses were conducted by means of the best evidence synthesis of van Peppen et al. Results: The methodological quality of the 10 included RCTs (677 patients) varied between four and eight points. Eight studies reported significant reduction in pain and/or disability by TSM. Overall, according to the best evidence synthesis, there is insufficient evidence that TSM is more effective than control interventions in reducing pain and disability in patients with non-specific neck pain. Conclusions: TSM has a therapeutic benefit to some patients with neck pain, when compared to the effect of interventions such as electrotherapy/thermal programme, infrared radiation therapy, spinal mobilization and exercises. However, in comparison to cervical spine manipulation, no evidence is found that TSM is more effective in reducing pain and disability. Implications for Rehabilitation TSM is often used in the treatment of non-specific neck pain, which is a major health problem in the Western society. There is insufficient evidence that TSM is more effective in reducing pain and disability than control treatments in patients with non-specific neck pain. Despite the insufficient evidence that TSM is more effective than control treatments, TSM has a therapeutic benefit to some patients with neck pain. Therefore, TSM alone or in combination with other interventions is a suitable intervention to use in the treatment of non-specific neck pain.