Background <p>Chemoradiotherapy is less tolerable for postoperative locoregional recurrent esophageal squamous cell carcinoma (ESCC).</p> Methods <p>ESCC patients with three or fewer locoregional recurrent lesions after radical surgery were enrolled. Anlotinib (12 mg, d1–14) was administered with radiotherapy (50.4–59.4 Gy) concurrently for two cycles, followed by sequentially for another two cycles. The primary endpoints were objective response rate (ORR) and toxicity.</p> Results <p>Between October 2019 and July 2022, 40 patients were eligible. The ORR was 90.0% (20.0% complete response, 70.0% partial response). The median local failure-free survival, distant metastasis-free survival, progression-free survival, and overall survival were 21.7 (95% CI, 7.839–35.627), 26.4 (95% CI, 17.706–35.028), 12.7 (95% CI, 4.023–21.377), and 29.9 months (95% CI, 18.543–41.323), respectively. Grade 3 adverse events occurred in only two patients (5.0%) who developed hypertension. No grade 4 treatment-related adverse events were observed.</p> Conclusions <p>The regimen of radiotherapy combined with anlotinib demonstrated high efficacy with tolerable toxicity in postoperative locoregional recurrent ESCC. This novel regimen provided a selectable treatment strategy for such patients, especially for those who cannot tolerate or refuse chemotherapy. Further randomised controlled trials are warranted.</p> Clinical trial registration <p>Chinese Clinical Trial Registry (ChiCTR1900025752).</p>