Purpose <p>The smallest worthwhile difference (SWD) represents the minimal beneficial effect of an intervention that patients consider valuable when weighed against its burdens, including potential harms, costs, and inconveniences. We aimed to determine the SWD for overactive bladder (OAB) treatment with beta-3 agonists and to evaluate the impact of trust in physicians on the SWD.</p> Methods <p>We recruited participants with symptoms suggestive of OAB in February 2025 through a research crowdsourcing service. The SWD for beta-3 agonists was estimated as a patient-required improvement in response rate to lifestyle modifications after three months using a benefit-harm trade-off approach. Trust in physicians was measured using the five-item Wake Forest Physician Trust Scale.</p> Results <p>Of 630 respondents, 472 who had symptom-related distress but were medication-naïve were included. Of these, 261 (55%) did not consider beta-3 agonist treatment worthwhile even if it achieved a 100% response. For the 211 participants willing to consider beta-3 agonists, the median SWD was a 20% improvement in response rate, with a wide interquartile range (5 to 40). In multivariable analysis, higher levels of trust in physicians were associated with smaller SWDs (mean difference per standard deviation, -4.11; 95% confidence interval, -7.00 to -1.22).</p> Conclusions <p>More than half of participants with symptoms suggestive of OAB and associated distress did not consider that beta-3 agonist treatment would be worthwhile given its burdens, even if there was a 100% response. Even among those willing to consider beta-3 agonists, the SWD varied substantially between individuals. Trust in physicians may influence SWD.</p> Running head <p>Smallest Worthwhile Difference of Beta-3 Agonists for Overactive Bladder.</p>