Purpose: We tested whether the potassium leak test predicts the outcome of therapy with heparinoids and antidepressants in interstitial cystitis. Materials and Methods: We retrospectively reviewed the records of 38 evaluable patients with interstitial cystitis who underwent a potassium leak test at the initial evaluation and who were treated intravesically with heparin or oral sodium pentosan polysulfate for a minimum of 6 months. All but 1 patient were also treated with tricyclic antidepressants. Changes in average pain score during voiding, urinary frequency and nocturia were evaluated. Results: The potassium leak test was positive and negative in 23 and 15 patients, respectively. There was no significant difference in the 2 groups at baseline in regard to the male-to-female ratio, patient age, years of symptoms, pain score, urinary frequency, nocturia or anesthetic capacity. After a minimum of 6 months of therapy patients in whom the potassium leak test was positive were more likely to have improvement than those in whom it was negative, as shown by a decrease of greater than 25% in pain score (78 versus 40%, p = 0.01), frequency (83 versus 47%, p = 0.02) and nocturia (83 versus 53%, p = 0.05). However, potassium leak test results showed no significant difference at the 50% decrease level in pain score, frequency or nocturia. Conclusions: The potassium leak test may predict outcome in patients with interstitial cystitis who are treated with combined heparinoid and tricyclic antidepressant medication.