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AIM: To compare postoperative complications and prognosis of esophageal squamous cell carcinoma pa- tients treated with different routes of reconstruction. METHODS: After obtaining approval from the Medi- cal Ethics Committee of the Sun Yat-Sen University Cancer Center, we retrospectively reviewed data from 306 consecutive patients with histologically diagnosed esophageal squamous cell carcinoma who were treated between 2001 and 2011. All patients underwent radical McKeown-type esophagectomy with at least two-field lymphadenectomy. Regular follow-up was performed in our outpatient department. Postoperative complica- tions and long-term survival were analyzed by treat- ment modality, baseline patient characteristics, and operative procedure. Data from patients treated via the retrosternal and posterior mediastinal routes were compared. RESULTS: The posterior mediastinal and retrosternal reconstruction routes were employed in 120 and 186 patients, respectively. Pulmonary complications were the most common complications experienced dur- ing the postoperative period (46.1% of all patients; 141/306). Compared to the retrosternal route, the pos- terior mediastinal reconstruction route was associated with a lower incidence of anastomotic stricture (15.8% vs 27.4%, P = 0.018) and less surgical bleeding (242.8±114.2 mL vs 308.2±168.4 mL, P 〈 0.001). The median survival time was 26.8 mo (range: 1.6-116.1 mo). Upon uni/multivariate analysis, a lower preopera- tive albumin level (P = 0.009) and a more advanced pathological stage (pT; P = 0.006; pN; P 〈 0.001) were identified as independent factors predicting poor prognosis. The reconstruction route did not influence prognosis (P = 0.477). CONCLUSION: The posterior mediastinal route of reconstruction reduces incidence of postoperative complications but does not affect survival. This route is recommended for resectable esophageal squamous cell carcinoma.