Purpose <p>External-beam radiation therapy is a treatment option for muscle-invasive bladder cancer (MIBC), which enables bladder preservation and is applicable to elderly or medically fragile patients. Since the accuracy of conventional intensity-modulated radiation therapy is vulnerable to even small daily changes, online adaptive radiation therapy (ART) may be a more appropriate option. This study aimed to evaluate the feasibility of cone-beam computed tomography (CBCT)-based online ART for MIBC in elderly or medically fragile patients.</p> Materials and methods <p>We applied CBCT-based online ART to treat two elderly patients with dementia and N0 M0 MIBC, who were deemed poor candidates for surgery or systemic therapies. A cumulative dose of 55&#xa0;Gy in 20 fractions over 4&#xa0;weeks was prescribed. Online ART was administered using Ethos™ Therapy.</p> Results <p>Both patients were able to follow the prescribed protocols with assistance (e.g., bladder voiding or filling and maintaining the treatment position), although full adherence was hindered by dementia. Nonetheless, they successfully completed the entire treatment regimen with manageable acute toxicities. The median treatment session duration was 23 (range 14–50, interquartile range 19–30) min. The median volume receiving at least 90% of the prescribed dose (V_90%) of the bowels was 1.25 (range 0.01–6.77) cm³ in the adapted plans and 24.78 (range 6.80–90.72) cm³ in the scheduled plan (<i>P</i> &lt; 0.001) in the first patient, and 0.13 (range 0.00–2.96) cm³ in the adapted plans and 9.60 (range 4.65–18.62) cm³ in the scheduled plan (<i>P</i> &lt; 0.001) in the second patient, respectively. A significant volume of the bowels was spared from receiving high doses in the adapted plans without compromising the target dose coverage.</p> Conclusions <p>CBCT-based online ART was considered a feasible therapeutic option for elderly or medically fragile patients with MIBC.</p>