OBJECTIVE: Drug-resistant trigeminal neuralgia (TN) can complicate the clinical course of patients affected by multiple sclerosis (MS). Various surgical procedures have been reported for the treatment of this condition, but there is no agreement on the best management of these patients. To our knowledge, there is no critical literature analysis focusing on this particular topic. The aim of this study was to evaluate the clinical outcome of different surgical procedures utilized for drug-resistant TN in MS patients. METHODS: We reviewed the literature about the studies reporting on surgical treatment of drug-resistant TN in MS patients. Case reports and case series less than 4 patients were excluded from the analysis. Nineteen studies were selected for the statistical analysis. To reduce the variability of the data, the selected studies were evaluated for the following outcome parameters: acute pain relief rate (APR), rate of recurrence (RR), pain free at follow-up rate (PF at FU) and complication rate (CR). For the statistical analysis, chi-square statistic, using the Fisher's exact test was utilized. RESULTS: There was no procedure statistically superior in terms of APR rate in MS patients following the surgical treatment of TN. The highest RR was observed for percutaneous balloon compression (PBC) (60.2±14.4%). This result was statistically significant when compared to gamma knife surgery (GKS) (p=0.0129) and microvascular decompression (MVD) (p=0.0281). MVD together with percutaneous radiofrequency rhizothomy (PRR) was associated with a statistically better PF at FU rate (56.5±16.8% and 73.5±14.2%, respectively). However PBC and MVD showed statistical significant minor CR compared to other techniques (no complications and 18.7±17.4%, respectively). CONCLUSION: Our study shows no differences in the short term results among different procedures for TN in MS patients. Each technique demonstrate advantages and limits in terms of long term pain, recurrence rate and complication rate. Each patient should be accurately informed on pros and cons of each procedure in order to be involved in the most appropriate choice.