To assess a flexible therapeutic strategy for patients referred to a specialized interstitial cystitis/bladder pain syndrome (IC/BPS) clinic using an individualized phenotype-directed treatment plan based on clinically based urinary, psychosocial, organ-specific, infection, neurologic or nonbladder, and tenderness of pelvic floor (UPOINT) categorization, instead of the traditional algorithmic stepwise approach.Consecutive patients referred to a specialized tertiary IC/BPS clinic with at least 1 follow-up posttreatment visit were categorized according to their UPOINT status and treated according to previously published individualized phenotype-based treatment plan. Patients were assessed at baseline and up to 2 years with validated symptom scores (interstitial cystitis symptom score [ICSI]; and pain urgency frequency questionnaire) as well as pain and voiding assessments.Follow-up visit data were available for 93 patients (mean age, 45.2 years; median age, 44 years; mean ICSI, 13.2 ± 3.6). Patients reported a median of 4 UPOINT domains (mean, 3.7 ± 0.94) with the following distribution: U = 100%; P = 31.2%; O = 97.8%; I = 45.2%; N = 39.8%; and T = 55.9%. The mean decrease in ICSI was 3.4 points. Significant clinical improvement (>30% decrease in ICSI) was observed in 46.2% compared with initial baseline visit. Pain urgency frequency, and pain and urgency scoring changes were comparable. No correlation between severity of symptoms and number of domains and ICSI decrease was observed.Almost 50% of patients referred to a tertiary IC/BPS clinic, regardless of the complexity or severity of condition, experienced clinically significant improvement using an individualized phenotype-directed therapeutic approach.