Background: Anlotinib has been approved in ESCC treatment because of its good tolerance and efficacy. Antiangiogenic target therapy plus immunotherapy has been initially recognized, whereas the data on the third & above line is still unknown. We aimed to retrospectively analyze the effect of anlotinib plus PD-1 inhibitor as later-line therapy on the survival of ESCC in the real world. (APEC, NCT 04984096). Methods: Retrospective data analysis was performed on ESCC patients (pts) treated with anlotinib plus PD-1 inhibitors as later-line therapy between Sep 2019 and Nov 2021 at Shanghai Chest Hospital, China. Demography, previous treatment, performance status, pathological classification, comorbidities, and distant metastatic organ status were collected. Progression free survival (PFS) was the primary end point of this study. The secondary end points were objective response rate (ORR), disease control rate (DCR) and overall survival (OS). Tumor response was assessed per RECIST version 1.1 by the investigators. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Results: There were 21 pts in the cohort. The average age was 61.5 (range 48-77) years old, and 95.2% patients were male. 7 cases (33.3%) had comorbidities. 2 cases (9.5%) had other tumor history. In addition, 19 pts (90.5%) had received radiotherapy, 21 pts (100.0%) had received chemotherapy and 19 pts (90.5%) had received immunotherapy. Among all pts, 1 patient achieved complete response (CR), 6 pts partial response (PR), 10 pts stable disease (SD), illustrating an ORR of 33.3 % and a DCR of 81.0%. Median PFS reached 8.1 months (95%CI 3.8-12.4) while median OS was not reached. All grades of TRAEs occurred in 95.2% pts and 90.5% were grade 1-2. Of note, grade 3-4 hematological toxicity (lymphocytopenia) was reported in only 2 patient (9.5%). All AEs were resolved after symptomatic treatment. Conclusions: Our data suggest that treatment with anlotinib plus PD-1 inhibitors as later-line therapy can result in curative effect of ESCC, which can achieve promising ORR, DCR and PFS with mild toxicity. To our knowledge, this is the first analysis to demonstrate the benefits of anlotinib plus PD-1 inhibitors as later-line therapy in ESCC. The data suggests that anlotinib plus PD-1 inhibitor is a new treatment in ESCC pts, and further validation in a larger cohort is needed. Clinical trial information: 04984096.