Background and objective <p>This study performed external validation by analyzing whether a combination of clinical parameters and urinary biomarker cluster could identify bladder-centric interstitial cystitis/bladder pain syndrome (IC/BPS) in a separate cohort of patients with lower urinary tract dysfunction (LUTD).</p> Methods <p>In total, 273 patients with LUTD were enrolled in this study. Thirteen urinary biomarkers were assayed. After excluding Hunner’s lesion disease and other confusable urological diseases, patients were diagnosed with IC/BPS and different LUTD subtypes, and the sensitivity and specificity for IC/BPS diagnosis were calculated according to urinary biomarker clusters and clinical parameters. The data were randomly divided into the training (80%) and testing (20%) datasets for model development and validation. A nomogram for identifying IC/BPS was then developed based on the training dataset.</p> Results <p>The patients were classified into the IC/BPS (n = 224) and non-IC/BPS LUTD (n = 49) groups. In total, 164 (86.3%) of 190 patients who met the urinary biomarker cluster criteria and 60 (72.3%) of 83 who did not were finally diagnosed with IC/BPS. The diagnostic accuracy of the urinary biomarker cluster was 0.648. After adding clinical parameters including age, bladder pain visual analog score, and IC Problem Index, the specificity and sensitivity reached 0.900 and 0.909, respectively, for the testing dataset. A nomogram for IC/BPS diagnosis was constructed based on these clinical and biomarker parameters. A total score of 96 could identify bladder-centric IC/BPS.</p> Conclusions and clinical implications. <p>External validation of urinary biomarker clusters plus clinical parameters has a good sensitivity and specificity for predicting bladder-centric IC/BPS in a cohort of patients with LUTD.</p>