The role of trigeminal ganglion percutaneous injection and radio-frequency lesioning procedures for the treatment of trigeminal neuralgia (TGN) in multiple sclerosis (MS) is well established. There is general acceptance that microvascular decompression (MVD) cannot be an appropriate treatment due to the view that the underlying aetiology is a demyelinating plaque affecting the root entry zone of the trigeminal pathway. Recently, MR-imaging has been used in the preoperative investigation of this group of patients demonstrating that neurovascular compression can occasionally be the responsible mechanism and that MVD can be the treatment of choice. We present five cases with MS and TGN. All the patients had failed to respond to medical treatment or percutaneous procedures. Magnetic resonance imaging demonstrated evidence of neurovascular compression in four cases. All the patients underwent MVD. Postoperatively four of the five patients made an uncomplicated recovery, were pain-free and fully satisfied with the result (mean follow-up 38.75 months; range 8-59 months). One patient developed recurrent pain 1 week following surgery and went on to have a total sensory rhizotomy. TGN in MS can be caused by neurovascular compression, which may be identified on MR-imaging. MVD has offered satisfactory short-term outcome for at least 2 years and does not inflict sensory loss. Longer follow-up will determine whether the outcome in MS patients will be as successful as in the TGN patients who do not suffer from MS.