For many years, spinal manipulation has been a popular form of treatment. Yet the debate about its clinical efficacy continues. The research question remains: Does spinal manipulation convey more than a placebo effect? To summarize the evidence from sham-controlled clinical trials of spinal manipulation as a treatment of various conditions, and to assess the methodological quality of these studies, a comprehensive search strategy was designed to locate all sham-controlled, double-blind, randomized trials of spinal manipulation as a treatment of any medical condition. Data were extracted from these trials and validated by two independent reviewers in a standardized fashion. All trials were critically analyzed and their methodological quality evaluated. Eight studies fulfilled the pre-defined inclusion/exclusion criteria. Three trials (two on back pain and one on enuresis) were judged to be burdened with serious methodological flaws. The results of the three most rigorous studies (two on asthma and one on primary dysmenorrhea) do not suggest that spinal manipulation leads to therapeutic responses which differ from an inactive sham-treatment. This analysis demonstrates that sham-controlled trials of spinal manipulation are sparse but feasible. The most rigorous of these studies suggest that spinal manipulation is not associated with clinically-relevant specific therapeutic effects.