Topical capsaicin is an established treatment option for various pain conditions. In a randomized double-blind multi-centre study, 281 patients suffering from chronic soft tissue pain were treated either with a cream containing capsaicin 0.05% ('Finalgon® CPDWärmecreme', n = 140) or placebo (n = 141). Of these, 151 were excluded from the ITT analysis, as they had in addition to their soft-tissue pain, pain of other origin. The primary outcome measure was a positive treatment response, defined as a pain sum score reduction of 30% or more. After 3 weeks of treatment, the median pain sum score had decreased by 49% (capsicum group) and 23% (placebo group) (ITT analysis, p = 0.0006). The odds ratio of the responders in favour for capsaicin was 4.3 (CI 97.5% lower limit 1.9, p < 0.0001). Improvements in the secondary efficacy measures confirmed the results. Likewise, all outcome measures had significantly more improved in the capsaicin-treated compared with the placebo-treated chronic back pain sufferers. All patients were included in the safety assessments. More adverse events occurred in the capsicum group (n = 13) than in the placebo group (n = 6). The capsaicin cream was generally well tolerated. The results indicate that capsaicin cream is useful in patients with chronic soft tissue pain and is also efficacious in patients with chronic back pain for which effectiveness was already demonstrated in earlier clinical trials.