BACKGROUND: Patients presenting with lower urinary tract symptoms (LUTS) are historically classified to several symptom clusters, primarily overactive bladder (OAB) and interstitial cystitis/bladder pain syndrome (IC/BPS). Accurate diagnosis, however, is challenging due to overlapping symptomatic features, and many patients do not readily fit into these categories. To enhance diagnostic accuracy, we previously described an algorithm differentiating OAB from IC/BPS. Herein, we sought to validate the utility of this algorithm for identifying and classifying a real-world population of individuals presenting with OAB and IC/BPS and characterize patient subgroups outside the traditional LUTS diagnostic paradigm. METHODS: An of 551 consecutive female subjects with LUTS evaluated in 2017 were administered 5 validated genitourinary symptom questionnaires. Application of the LUTS diagnostic algorithm classified subjects into controls, IC/BPS, and OAB, with identification of a novel group of highly bothered subjects lacking pain or incontinence. Symptomatic features of this group were characterized by statistically significant differences from the OAB, IC/BPS and control groups on questionnaires, comprehensive review of discriminate pelvic exam, and thematic analysis of patient histories. In a of 215 subjects with known etiologies of their symptoms (OAB, IC/BPS, asymptomatic microscopic hematuria, or myofascial dysfunction confirmed with electromyography), significant associations with myofascial dysfunction were identified in a multivariable regression model. Pre-referral and specialist diagnoses for subjects with myofascial dysfunction were catalogued. FINDINGS: Application of a diagnostic algorithm to an unselected group of 551subjects presenting for urologic care identified OAB and IC/BPS in 137 and 96 subjects, respectively. An additional 110 patients (20%) with bothersome urinary symptoms lacked either bladder pain or urgency characteristic of IC/BPS and OAB, respectively. In addition to urinary frequency, this population exhibited a distinctive symptom constellation suggestive of myofascial dysfunction characterized as "persistency": bothersome urinary frequency resulting from bladder discomfort/pelvic pressure conveying a sensation of bladder fullness and a desire to urinate. On examination, 97% of persistency patients demonstrated pelvic floor hypertonicity with either global tenderness or myofascial trigger points, and 92% displayed evidence of impaired muscular relaxation, hallmarks of myofascial dysfunction. We therefore classified this symptom complex "myofascial frequency syndrome". To confirm this symptom pattern was attributable to the pelvic floor, we confirmed the presence of "persistency" in 68 patients established to have pelvic floor myofascial dysfunction through comprehensive evaluation corroborated by symptom improvement with pelvic floor myofascial release. These symptoms distinguish subjects with myofascial dysfunction from subjects with OAB, IC/BPS, and asymptomatic controls, confirming that myofascial frequency syndrome is a distinct LUTS symptom complex. INTERPRETATION: This study describes a novel, distinct phenotype of LUTS we classified as in approximately one-third of individuals with urinary frequency. Common symptomatic features encompass elements in other urinary syndromes, such as bladder discomfort, urinary frequency and urge, pelvic pressure, and a sensation of incomplete emptying, causing significant diagnostic confusion for providers. Inadequate recognition of myofascial frequency syndrome may partially explain suboptimal overall treatment outcomes for women with LUTS. Recognition of the distinct symptom features of MFS (persistency) should prompt referral to pelvic floor physical therapy. To improve our understanding and management of this as-yet understudied condition, future studies will need to develop consensus diagnostic criteria and objective tools to assess pelvic floor muscle fitness, ultimately leading to corresponding diagnostic codes. FUNDING: This work was supported by the AUGS/Duke UrogynCREST Program (R25HD094667 (NICHD)) and by NIDDK K08 DK118176 and Department of Defense PRMRP PR200027, and NIA R03 AG067993.