Background and purpose: We evaluated and compared the efficacy and safety of chemotherapy with paclitaxel plus cisplatin (TP) or carboplatin (TC) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) who underwent neoadjuvant chemoradiotherapy (NCRT). Materials and methods: This single-center retrospective study assessed patients with LA-ESCC (cT2N + M0, cT3-4aNanyM0) receiving NCRT plus curative-intent esophagectomy with TP or TC regimen. The primary endpoints were grade >= 3 adverse events (AEs) and overall survival (OS). AEs were compared using a t-test according to CTCAE 4.0. The Kaplan-Meier survival curves were compared using the log-rank test; the treatment effect was measured using hazard ratios and 95% confidence intervals. Results: We included 151 and 50 patients in the TC and TP groups, respectively. Baseline demographic and clinical characteristics were well balanced between groups. The TP group exhibited significantly higher hematologic and non-hematologic AEs than the TC group, and the noticeable difference was the incidence of febrile neutropenia of grade 3 or higher (P = 0.011). No significant intergroup differences were noted considering postoperative complications, resection margins, or pathological complete remission rate (all P > 0.05). OS and progression-free survival (PFS) did not significantly differ between groups. The estimated 3-year OS and PFS rates were 65.1% versus 69.4% and 58.4% versus 53.5% for TP and TC groups, respectively. Conclusion: In patients with LA-ESCC, we recommend TC, not TP, as an optimal chemotherapy regimen for NCRT, given its superiorsafety profile and comparable efficacy.