Purpose <p>To investigate the efficacy and safety of acupuncture combined with mirabegron for overactive bladder (OAB) treatment.</p> Methods <p>This prospective cohort study took place at Ganzhou People’s Hospital. One hundred and sixty patients with OAB were divided into control and treatment groups at a ratio of 1:1 using a randomized number-table method. The control group was administered mirabegron alone (50&#xa0;mg/day), while the treatment group was administered mirabegron orally and acupuncture at Guanyuan (CV4), Zhongji (CV3), and Sanyinjiao (SP6). The Overactive Bladder Syndrome Score (OABSS), voiding, urgency, nocturia, incontinence, and incidence of related adverse events were compared between the two groups at baseline and after 4, 8, and 12&#xa0;weeks of treatment.</p> Results <p>Of the160 patients, 10 were lost; the remaining 74 and 76 patients were included in the control and treatment groups, respectively. The mean numbers of occurrences of voiding, urgency, nocturia, and incontinence along with OABSS of the patients in the two groups improved after 4, 8, and 12&#xa0;weeks of treatment compared with those before treatment, with the therapeutic effect more significant in the treatment group (<i>P</i> &lt; 0.05). The overall efficacy rates in the control and treatment groups were 81.08% and 94.74%, respectively (<i>P</i> = 0.022). The incidence of total adverse events was not significantly different between groups after 12&#xa0;weeks of treatment (<i>P</i> &gt; 0.05); no serious adverse reactions occurred in either group.</p> Conclusions <p>Acupuncture combined with mirabegron was effective for OAB treatment. This treatment combination was superior to mirabegron alone without significant increases in adverse effects.</p> Trial registration <p>This study was registered at <a href="http://www.chictr.org">www.chictr.org</a> (NCT06181019).</p>