Objective <p>To evaluate the efficacy and safety of combining flexible ureteroscopy (FURS) with potassium sodium hydrogen citrate(PSHC) for the treatment of 20–30&#xa0;mm uric acid renal stones.</p> Methods <p>A retrospective analysis of outcomes of patients with 20–30&#xa0;mm uric acid renal stones who were treated with FURS and holmium lithotripsy was conducted between July 2021 and May 2024. Of them, 60 patients accepted FURS combined potassium sodium hydrogen citrate(PSHC) therapy while 70 patients underwent the FURS procedure alone. The demographic data, stone characteristics, surgical details, and perioperative outcomes of the patients were assessed retrospectively. Stone-free status was defined as the complete absence of stones on computed tomography.</p> Results <p>Totally 130 patients were enrolled and analyzed in this study. No significant differences were found between the two groups in terms of gender, age, body mass index, comorbidities, stone burden, stone density, number of stones, or laterality. The mean operation time, American Society of Anesthesiologists (ASA) score, postoperative stay, and complication rate were also similar between the groups. The combined group incurred higher costs (<i>p</i> &lt; 0.01),but it achieved significantly higher stone-free rate and Wisconsin Stone Quality of Life Questionnaire score at 4 weeks post-operatively (<i>96.7%</i> vs. <i>85.7%</i>,<i>p</i> = 0.029;124.63 vs. 114.44,<i>p</i> &lt; 0.01). Additionally, the combined group had a significantly higher urine pH at 4 weeks postoperatively compared to the non-combined group (6.63 vs. 5.50, <i>p</i> &lt; 0.01).</p> Conclusion <p>Compared to a single procedure, FURS combined with PSHC therapy is an effective and safe treatment for 20–30&#xa0;mm uric acid renal stones.</p>