Background <p>Intravesical gemcitabine is widely used for non-muscle-invasive bladder cancer (NMIBC) due to its favorable safety profile. While transient irritative symptoms are common, persistent inflammatory cystitis remains poorly characterized.</p> Methods <p>We conducted a retrospective observational study at a tertiary referral center. Patients receiving intravesical gemcitabine following transurethral resection of bladder tumor (TURBT) between 2022 and 2024 were screened using a stringent operational definition: (1) irritative symptoms lasting ≥ 8 weeks; (2) persistent sterile pyuria with negative urine cultures; (3) cystoscopic inflammatory changes (follicular elevations with diffuse hyperemia); (4) absence of tumor recurrence; (5) failure of conservative therapy; and (6) histopathological confirmation. Clinical characteristics and outcomes following conversion to mitomycin C (MMC) were analyzed.</p> Results <p>Among 101 patients treated with intravesical gemcitabine, two (1.98%) met the predefined criteria. Patient A (70-year-old female) developed persistent urinary frequency, urgency, and dysuria lasting 4 months. Patient B (30-year-old male) experienced similar symptoms lasting 3 months. Both presented with sterile pyuria, microscopic hematuria, and cystoscopic findings of follicular elevations with diffuse hyperemia. Biopsy confirmed chronic inflammatory infiltration with lymphoid follicle formation. Following discontinuation of gemcitabine and conversion to MMC, both patients experienced complete symptomatic resolution within 6–8 weeks, with marked attenuation of inflammatory cystoscopic findings.</p> Conclusions <p>Persistent follicular cystitis following intravesical gemcitabine is a rare but clinically significant entity. Early recognition and therapeutic conversion to MMC can prevent prolonged morbidity. Larger studies are warranted to determine incidence and risk factors.</p>