Objective:In this post-hoc analysis, we evaluated anlotinib treatment-induced hypertension as a potential predictive factor of efficacy in esophageal squamous cell carcinoma (ESCC) patients. Methods:A total of 109 patients enrolled in the anlotinib group in a phase 2 trial were included. The tumor response was assessed by computed tomography at week 3, week 6, and then every 6 weeks until progressive disease was observed. The primary endpoint of the study was progression free survival (PFS). The secondary endpoints included overall survival (OS) and objective response rate (ORR). Results:In all patients, the median PFS was 3.02 months [95% confidence interval (CI):2.63-3.65 months] and the OS was 6.11 months (95% CI:4.40-7.79 months). The ORR was 7.34% (95% CI:3.22%-13.95%). A total of 59 (54%) patients were diagnosed with treatment-induced hypertension (Group A), and the remaining patients (n = 50, 46%) were in Group B. Baseline prognostic factors were similar between the 2 groups. Patients in Group A had a longer PFS and OS and higher ORR. When stratifying patients using a previously known history of hypertension, treatment-induced hypertension was a predictor only for patients without previous hypertension, who had longer PFS [hazard ratio (HR):0.40, 95% CI:0.24-0.68] and OS (HR:0.37, 95% CI:0.21-0.67). Conclusions:We showed, for the first time, a correlation between treatment-induced hypertension and better prognoses in recurrent or metastatic ESCC patients treated with anlotinib, without a previously known history of hypertension. Treatment-induced hypertension may be a simple and low cost predictor for anlotinib antitumor efficacy in these patients, which may also reflect the intended target inhibition.