Objective To evaluate the discomfort and long-term efficacy associated with instillation of dimethyl sulfoxide (DMSO). Material and Methods A total of 28 patients, 13 (11 females, 2 males) with classic interstitial cystitis (IC) and 15 (13 females, two males) with non-ulcer disease, who had received at least one series of six instillations of DMSO were studied. In addition to studying micturition diaries before and after the treatment, the evaluation included assessments of pain using a visual analog scale and of side-effects after each instillation in every series. Data were obtained by surveying the clinical records. A follow-up telephone interview was conducted for those patients who were treated with DMSO and in whom the treatment was considered successful. DMSO instillations were considered successful if the patient reported symptom amelioration and chose to continue with the treatment. Results Side-effects were not more common or pronounced in patients with classic compared to non-ulcer IC. For classic IC a significant difference could be seen when comparing side-effects experienced during the first three instillations and the three subsequent instillations. After DMSO instillations, a residual treatment effect lasting 16–72 months could be seen. Conclusions Intravesical instillation therapy with DMSO appears to be a feasible treatment option for both subtypes of IC and is associated with a reasonably low degree of discomfort.