Background: Serum α-1-acid glycoprotein (AAG) level was an independent predictor of response and a prognostic factor of survival in patients with non-small cell lung cancer treated with docetaxel chemotherapy. However, it has not been determined whether AAG is associated with the outcomes of esophageal cancer patients who have been treated with a combination of docetaxel, cisplatin and 5-fluorouracil (DCF) as neoadjuvant therapy. Methods: This retrospective study included a cohort of 39 patients with clinical stage II/III esophageal cancer, based on the International Union Against Cancer TNM classification system 7th edition, who were treated with neoadjuvant DCF followed by surgery. DCF consisted of docetaxel (70mg/m²) and cisplatin (70mg/m²) on day 1, and continuous infusion of 5-fluorouracil (750mg/m²/day) on days 1-5, with this regimen repeated every 3 weeks up to three cycles. Patients were divided into groups by median value of baseline AAG levels. Patient characteristics, preoperative clinical stage, chemotherapy effect, and survival were compared between the high and low AAG groups. Results: The clinical stage IIA, IIB, IIIA, IIIB and IIIC were 4, 4, 14, 17 and 0, respectively. The completion rate of three cycles of chemotherapy was 76.9% (30/39). All patients underwent surgery and the R0 resection rate was 97.4% (38/39). The best overall response rate of DCF was 48.7% with a pathological complete response of 5.1%. The 2-year progression-free survival and overall survival (OS) rates were 60.5% and 76.9%, respectively. The median serum AAG was 95 g/L, ranging from 57 to 228 g/L. A trend of lower response rate (35.0% vs. 57.9%; P = 0.20) and shorter OS (median not reached; hazard ratio [HR] 2.08; P = 0.24) was observed in patients with a high AAG level (AAG > 95 g/L) compared with a low AAG level (AAG ≦ 95 g/L). Multivariate analysis showed an AAG level hazard ratio of 1.60 (P = 0.59) for OS. Conclusions: There was a trend toward improved response and survival with low serum AAG level, for patients with esophageal cancer who received neoadjuvant DCF chemotherapy.