Background: Cervical spine manipulation (CSM) is a commonly utilized intervention, but its use remains controversial.Purpose: To retrospectively analyze all available documented case reports in the literature describing patients who had experienced severe adverse events (AEs) after receiving CSM to determine if the CSM was used appropriately, and if these types of AEs could have been prevented using sound clinical reasoning on the part of the clinician. Data sources: PubMed and the Cumulative Index to Nursing and Allied Health were systematically searched for case reports between 1950 and 2010 of AEs following CSM. Study selection: Case reports were included if they were peer-reviewed; published between 1950 and 2010; case reports or case series; and had CSM as an intervention. Articles were excluded if the AE occurred without CSM (e.g. spontaneous); they were systematic or literature reviews. Data extracted from each case report included: gender; age; who performed the CSM and why; presence of contraindications; the number of manipulation interventions performed; initial symptoms experienced after the CSM; and type of resultant AE. Data synthesis: Based on the information gathered, CSMs were categorized as appropriate or inappropriate, and AEs were categorized as preventable, unpreventable, or unknown. Chi-square analysis with an alpha level of 0.05 was used to determine if there was a difference in proportion between six categories: appropriate/preventable, appropriate/unpreventable, appropriate/unknown, inappropriate/ preventable, inappropriate/unpreventable, and inappropriate/unknown. Results: One hundred thirty four cases, reported in 93 case reports, were reviewed. There was no significant difference in proportions between appropriateness and preventability, P5.46. Of the 134 cases, 60 (44.8%) were categorized as preventable, 14 (10.4%) were unpreventable and 60 (44.8%) were categorized as 'unknown'. CSM was performed appropriately in 80.6% of cases. Death resulted in 5.2% (n57) of the cases, mostly caused by arterial dissection. Limitations: There may have been discrepancies between what was reported in the cases and what actually occurred, since physicians dealing with the effects of the AE, rather than the clinician performing the CSM, published many of the cases. Conclusions: This review showed that, if all contraindications and red flags were ruled out, there was potential for a clinician to prevent 44.8% of AEs associated with CSM. Additionally, 10.4% of the events were unpreventable, suggesting some inherent risk associated with CSM even after a thorough exam and proper clinical reasoning.