Introduction <p>Postherpetic neuralgia (PHN) frequently coexists with depression and remains associated with poor clinical outcomes despite interventional neuromodulation. Repetitive transcranial magnetic stimulation (rTMS) may lower the incidence of poor prognosis in this population. The aim of this trial was to evaluate the effect of perioperative rTMS in patients with PHN and comorbid depression undergoing neuromodulation.</p> Methods <p>This randomized, single-center, sham-controlled trial was conducted at the First Affiliated Hospital of Soochow University in Jiangsu Province from February 2025 to November 2025. A total of 174 participants were randomly assigned, stratified by neuromodulation therapy, to receive either 10 Hz rTMS (<i>n</i> = 87) or sham stimulation (<i>n</i> = 87) targeting the primary motor cortex for five consecutive days. The primary outcome was the incidence of poor prognosis at 3 months.</p> Results <p>The incidence of poor prognosis was significantly lower in the rTMS group compared with the sham group (27.4% versus 42.7%; odds ratio [OR] 0.51; 95% confidence interval [CI] 0.27–0.97; <i>P</i> = 0.039), corresponding to an absolute risk reduction of 15.3%. After adjusting for potential confounders, patients in the rTMS group were less likely to experience poor prognosis at 3 months than those in the sham group (adjusted OR, 0.47; 95% CI 0.23–0.95; <i>P</i> = 0.036).</p> Conclusions <p>In this randomized controlled trial, perioperative rTMS reduced the risk of unfavorable clinical outcomes in patients with PHN and comorbid depression undergoing neuromodulation, without compromising safety. These findings support rTMS as a promising adjunctive therapeutic strategy in this population.</p> Trial Registration <p>Chinese Clinical Trial Register Identifier: ChiCTR2500096978.</p>