Objective: Controversy surrounds the safety of cervical spine manipulation. Ischemic stroke secondary to cervical spine manipulation is a hypothesized adverse event. In Canada, the seriousness of these events and their perceived association to cervical spine manipulation has led some members of the public to call for a ban of the procedure. The primary objective of this study was to determine the incidence of internal carotid artery (ICA) dissection after cervical spine manipulation in patients who experience neck pain and its associated disorders. The secondary objective was to determine whether cervical spine manipulation is associated with an increased risk of ICA dissection in patients with neck pain, upper back pain, or headaches. Methods: We systematically searched MEDLINE, CINAHL, Alternative Health, AMED, Index to Chiropractic Literature, and EMBASE from 1970 to November 2012. Two independent reviewers used standardized criteria to screen the eligibility of articles. We considered cohort studies, case-control studies, and randomized clinical trials that addressed our objectives. We planned to critically appraise eligible articles using the Scottish Intercollegiate Guideline Network methodology. Results: We did not find any epidemiologic studies that measured the incidence of cervical spine manipulation and ICA dissection. Similarly, we did not find any studies that determined whether cervical spine manipulation is associated with ICA dissection. Conclusions: The incidence of ICA dissection after cervical spine manipulation is unknown. The relative risk of ICA dissection after cervical spine manipulation compared with other health care interventions for neck pain, back pain, or headache is also unknown. Although several case reports and case series raise the hypothesis of an association, we found no epidemiologic studies that validate this hypothesis.