BACKGROUND The impact of body mass index (BMI) on survival in patients with esophageal squamous cell carcinoma (ESCC) undergoing surgery remains unclear. Therefore, a definition of clinically significant BMI in patients with ESCC is needed. OBJECTIVE To explore the impact of preoperative weight loss (PWL)-adjusted BMI on overall survival (OS) in patients undergoing surgery for ESCC. METHODS This retrospective study consisted of 1545 patients who underwent curative resection for ESCC at West China Hospital of Sichuan University between August 2005 and December 2011. The relationship between PWL-adjusted BMI and OS was examined, and a multivariate analysis was performed and adjusted for age, sex, TNM stage and adjuvant therapy. RESULTS Trends of poor survival were observed for patients with increasing PWL and decreasing BMI. Patients with BMI ≥ 20.0 kg/m2 and PWL < 8.8% were classified into Group 1 with the longest median OS (45.3 mo). Patients with BMI < 20.0 kg/m2 and PWL < 8.8% were classified into Group 2 with a median OS of 29.5 mo. Patients with BMI ≥ 20.0 kg/m2 and PWL ≥ 8.8% (HR = 1.9, 95%CI: 1.5-2.5), and patients with BMI < 20.0 kg/m2 and PWL ≥ 8.8% (HR = 2.0, 95%CI: 1.6-2.6), were combined into Group 3 with a median OS of 20.1 mo. Patients in the three groups were associated with significantly different OS (P < 0.05). In multivariate analysis, PWL-adjusted BMI, TNM stage and adjuvant therapy were identified as independent prognostic factors. CONCLUSIONS PWL-adjusted BMI has an independent prognostic impact on OS in patients with ESCC undergoing surgery. BMI might be an indicator for patients with PWL < 8.8% rather than ≥ 8.8%.