This article presents and evaluates the symptoms, presentation, diagnosis, and treatment of men with interstitial cystitis (IC). A retrospective chart review and an interview of all men in our practice diagnosed with IC since 1990 was performed. The patients’ presenting symptoms, physical findings, clinical evaluation, and responses to therapy were reviewed. A total of 52 men were identified during the study who met the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) criteria for diagnosis of IC. The most common referral diagnosis was prostatitis with the most common predominant symptoms being suprapubic pain with urinary frequency and dysuria. A significant number of male patients also developed sexual dysfunction. All patients met the NIDDK criteria for a diagnosis of IC. Multiple therapies were used for the treatment of these patients over the study period. Five patients were initially treated with dimethyl sulfoxide (DMSO) as a sole agent; however, all intravesically treated patients eventually failed this form of therapy. A total of 37 of 52 patients were treated with multidrug oral therapy. Findings showed that 80% of patients achieved >75% improvement in their symptomology at 6 months of follow-up with a durable response at 1 year. IC in men is probably underdiagnosed and is most commonly misdiagnosed as prostatitis. The patient’s presentation is analogous to that in the female population allowing for gender differences. The patients responded well to multidrug oral therapy.