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To evaluate the efficacy and safety of pentosan polysulfate sodium (PPS) in relieving symptoms of interstitial cystitis, the authors retrospectively reviewed charts of 260 patients in whom interstitial cystitis had been diagnosed. Subsequently, they conducted a follow-up phone interview or mail survey of those patients who were treated with PPS to investigate changes in the patients' symptoms, adverse effects, and change in quality of life. The control group consisted of patients whose interstitial cystitis had been diagnosed at cystoscopy and had a duration of at least 1 year and who had taken at least one or more oral medications for their symptoms. The average length of treatment was 9.3 months among the 27 subjects on PPS therapy. The mean length of time that they had diagnosed interstitial cystitis was 35.63 months and 48.78 months for the PPS-treated and control groups, respectively, with no statistically significant difference. Changes in frequency, urgency, and pain were greater in the treatment group and statistically significant (P = .11, P = .49, and P = .004, respectively). No change occurred in the rate of nocturia in the PPS-treated group compared with that in the control group. Symptoms of both groups improved over time, but improvement was statistically significantly greater in the treatment group (P = .001) over the treatment interval. The most common side effect attributable to PPS was diarrhea in 15% of subjects. Pentosan proved to be an efficacious option for reducing the debilitating symptoms of interstitial cystitis.