Background: Painful bladder syndrome/interstitial cystitis (PBS/IC) is defined as a syndrome of urgency, frequency, and suprapubic pain in the absence of positive urine culture or obvious bladder pathology. As no specific etiology has been identified yet, no specific methodology exists for diagnosis of this condition. One potential etiology of PBS/IC is inflammation of the bladder mucosa associated with abnormal angiogenesis and ulcerative lesions. The purpose of this study was to examine the feasibility of using transcutaneous near infrared spectroscopy (NIRS) of the bladder to monitor tissue oxygenation and hemodynamics as a means of differentiating subjects diagnosed with PBS/IC from those with other bladder conditions. Methods: Twenty-four adult patients with lower urinary tract dysfunction were divided into 2 groups, PBS/IC and non-PBS/IC after standard diagnostic investigations. Detrusor oxygen saturation percentage (TSI%) was measured in all subjects while they were at rest in a supine position, using a spatially resolved (SR) NIRS instrument. Mean values of detrusor TSI% were significantly different between the two groups (74.2%±4.9 in PBS/IC vs. 63.6%±5.5 in non-PBS/IC, P<0.0005). Results: Noninvasive NIRS interrogation of the bladder demonstrated that patients diagnosed as having PBS/IC had significantly higher detrusor oxygen saturation at rest. Conclusions: SR-NIRS as a feasible non-noninvasive entity for use in the evaluation of patients for the presence or absence of physiologic changes associated with PBS/IC. © 2013 SPIE.