Background <p>Bladder outlet obstruction mediated underactive bladder represents a challenging condition in which transurethral resection of prostate did not prove to be a sufficient treatment option. Therefore, this study was conducted to evaluate the effects and adverse effects of Pyridostigmine as a treatment for underactive bladder after transurethral resection of prostate.</p> Methods <p>This prospective, double-blind, randomized controlled study was conducted between May 2024 and November 2024. Sixty-six patients who had benign prostatic hyperplasia with preoperative underactive bladder and eligible for transurethral resection of prostate were randomized into two groups: the Pyridostigmine group, which received Pyridostigmine 120&#xa0;mg daily for 3 months postoperatively, and the control group, which received placebo postoperatively. Patients were followed-up for 3 months postoperatively to observe symptom changes, urodynamic changes and adverse effects.</p> Results <p>Patient who received Pyridostigmine showed significant improvement compared to the control group patients regarding IPSS score (<i>p</i> = 0.001), quality of life (<i>p</i> &lt; 0.001), postvoid residual volume (<i>p</i> = 0.002), maximum flow rate (<i>p</i> &lt; 0.001), contractility index (<i>p</i> = 0.001) and postoperative retention incidence (<i>p</i> = 0.005). Mild adverse effects were reported in 23.5% of patients who received Pyridostigmine with no reported serious adverse effects.</p> Conclusion <p>Pyridostigmine after transurethral resection of prostate in patients with underactive bladder with benign prostatic hyperplasia leads to significant improvements in postoperative subjective and objective outcomes with insignificant adverse effects and wide safety profile making Pyridostigmine a therapeutic option for enhancing bladder function recoverability after transurethral resection of prostate.</p>