The use of spinal cord stimulation (SCS) has been advocated for the management of ischemic pain and the prevention of amputations in patients with inoperable critical limb ischemia (CLI), although data on benefit are conflicting. Several reports described apparently differential treatment effects in subgroups. The purpose of this study was to analyze the data on the efficacy of SCS and to clarify preselection issues. Five randomized trials have been performed with a total number of 332 patients. Primary outcome measures were mortality and limb survival. In the largest multicenter randomized trial (n = 120), which compared SCS treatment and best medical treatment alone in patients with inoperable CLI, we determined the incidence of amputation and its relation to various predefined risk factors. We used Kaplan-Meier and Cox regression analyses to quantify prognostic effects and differential treatment effects. Meta-analysis yielded a relative risk for amputation of 0.79 and a risk difference of -0.07 (p = 0.15). The risk factor analysis clearly showed that patients with ischemic skin lesions (ulcerations or gangrene) had a worse prognosis (i.e., higher risk of amputation) (relative risk 2.30, p = 0.01). We did not observe significant interactions between this prognostic factor (or any other) and the effect of SCS. The analysis did not indicate a subgroup of patients who might specifically be helped by SCS. Meta-analysis including all randomized data shows insufficient evidence for higher efficacy of SCS treatment compared with best medical treatment alone. Although some factors provide prognostic information as to the risk of amputation in patients with CLI, there are no data supporting a more favorable treatment effect in any group.