Abstract: Objective To compare the recurrence patterns and survival outcomes of immune checkpoint inhibitors (ICIs) combined with chemoradiotherapy versus chemoradiotherapy alone in the treatment of locally advanced, inoperable esophageal squamous cell carcinoma (ESCC). Methods Retrospective analysis was conducted on 167 patients with locally advanced, inoperable ESCC who received initial treatment at the Affiliated Hospital of Xuzhou Medical University from January 2019 to December 2023. According to the treatment regimen, the patients were divided into an immune group (n=81) and a non-immune group (n=86). Recurrence patterns and survival outcomes were compared. In the whole population, the recurrence patterns of the synchronous chemoradiotherapy plus immunotherapy group (n=29) and the synchronous chemoradiotherapy group (n=31) were compared. Within the immune group, patients were further divided based on the timing of immune therapy relative to radiotherapy into a pre-radiotherapy group (n=30), a during-radiotherapy group (n=29), and a post-radiotherapy group (n=22), and recurrence patterns were compared. Results In the whole population, the most common recurrence type in both the immune and non-immune groups was primary local recurrence, but the recurrence rate in the immune group was significantly lower than in the non-immune group (39.5% vs 57.0%, P=0.024). The non-immune group had a higher proportion of isolated non-regional lymph node recurrence (13.6% vs 26.7%, P=0.035). Survival analysis showed that the median progression-free survival (PFS) in the immune group was significantly longer than in the non-immune group (29.5 vs 10.5 months, P<0.001). The overall survival (OS) showed an extended trend in the immune group, but this did not reach statistical significance (P=0.072). The 2-year OS rates in the immune group were significantly higher than in the non-immune group (P<0.05). Subgroup analysis showed no statistically significant differences in recurrence patterns between the synchronous chemoradiotherapy plus immunotherapy group and the synchronous chemoradiotherapy group, as well as among different immune intervention timings within the immune group. Conclusions Compared to chemoradiotherapy alone, ICIs combined with chemoradiotherapy significantly reduces the risk of local and non-regional lymph node recurrence and significantly prolongs PFS in patients with locally advanced, inoperable ESCC, with a trend toward improvement in OS.