OBJECTIVE: The aim of this study was to determine the cost-effectiveness of Acetylcysteïne and DMSO in the treatment of patients with reflex sympathic dystrophy (RSD). METHODS: The study was a prospective, double-dummy, double blind, controlled trial. Patients were followed for one year. The primary outcome measure was the Impairment-level Sum Score (ISS). Cost data were prospectively collected using cost-diaries. Utilities were determined using the EuroQol. Both cost-effectiveness and cost-utility analyses were performed. Differences in mean direct, indirect and total costs between groups were estimated with corresponding 95% Confidence Intervals (CI). Also cost-effectiveness and cost-utility ratios with corresponding 95% CI were calculated using bootstrapping techniques. RESULTS: There was a statistically significant difference in effect (ISS). DMSO generated more reduction than Acetylcysteïne (diff:1.82 CI:-4.90;-1.27 ). This significant difference appeared also in the subgroup of patients with warm RSD. The total costs were statistically significant lower in the DMSO compared to the Acetylcysteïne group (diff: 2866 CI: 666;5179). This significant difference was also found in the subgroup of patients with warm RSD. The cost-effectiveness and cost-utility ratios showed that DMSO is dominant over Acetylcysteïne. CONCLUSION: In general, DMSO is the preferred method of treatment for patients with RSD. There are some indications that Acetylcisteïne may be more cost-effective for cold RSD, but this was found in a small subgroup only and should be confirmed in a larger trial.