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Introduction The comprehensive complication index (CCI) is a new index to comprehensively and systematically evaluate complication severity. The objective of this study was to evaluate the predictive ability of CCI on short—and long-term overall survival(OS) in patients with esophageal squamous cell carcinoma (ESCC) undergoing minimally invasive esophagectomy (MIE) based on a propensity Score Matching (PSM) analysis. Methods A total of 356 patients treated with radical MIE from 2013 to 2017 were included, and the primary outcome was OS, and the secondary outcomes were postoperative hospital stay and hospital costs. Firstly, the optimla cut-off value of CCI was determined by X-tile. PSM was used to balance the baseline characteristics. Second, we compared postoperative hospital stay and hospital costs between high- and low-CCI group. Third, the Kaplan–Meier survival curve was used to analyze survival difference. Fourth, univariate and multivariate Cox analysis was used to explore the independent risk factors of OS. Results The CCI > 24.2 was defined as high-CCI group and CCI≦24.2 was defined as low-CCI group. The high-CCI group had more hospital costs and longer hospital stay than the low-CCI group both before and after PSM (p < 0.001). The K-M analysis indicated that patients with high CCI had worse prognosis both before and after PSM (before matching: P < 0.001; after matching: P = 0.04). CCI was determined as independent prognostic factor both before and after PSM (before PSM, P = 0.002; after PSM, P = 0.025). Conclusion The CCI could quantify postoperative complications after esophagectomy. High CCI is associated with longer hospital stay and hospitalization costs, and is an independent risk factor for poor OS. [ABSTRACT FROM AUTHOR]