Background: Neoadjuvant chemotherapy with docetaxel, cisplatin plus 5-FU (Neo DCF) is one of the standard treatment for resectable esophageal cancer (EC) based on the results of the JCOG1109 study, however, a high frequency (5-30%) of febrile neutropenia (FN) has been reported with NeoDCF and the elderly (patients) pts have higher risk for FN. A single arm phase II study indicated that use of primary prophylactic pegfilgrastim (PG) on day 3 of NeoDCF might prevent FN. We compared the frequency of neutropenia and FN with or without primary prophylactic administration of PG on day 3 of NeoDCF in elderly resectable EC pts. Methods: EC pts who had received NeoDCF between 2009 and 2022, were ≥70 years old, and had adequate organ functions and PS were selected for this retrospective study. Pts were divided into two groups with Day 3 PG-containing DCF (day3 prophylactic PG: D3PG) or No PG DCF (non-prophylactic PG: NPG). Three courses of DCF (DTX [day 1]: 70 mg/m², CDDP [day 1]: 70 mg/m², 5-FU [continuous infusion on days 1-5]: 750 mg/m², every 3 weeks) were planned, and prophylactic antibiotics was administered on days 5-15 in each group if possible. We retrospectively evaluated the relative dose intensity (RDI), histopathological and clinical benefit, and adverse events. Results: A total of 67 pts (D3PG, 32; NPG, 35) with a median age of 73 years were identified. The PS (0/1/2) and clinical stage (I-II/III/ IVA-B [only supraclavicular lymph node]) were 18 (56.3%)/12 (37.5%)/2 (6.2%) and 1 (3.1%)/18 (56.3%)/13 (40.6%) in the D3PG group and 20 (57.1%)/15 (42.9%)/0 and 7 (20.0%)/24 (68.6%)/4 (11.4%) in the NPG group, respectively. Six pts in the D3PG group and 3 pts in the NPG group discontinued NeoDCF because of toxicity and progression. All pts except 1 in the D3PG group underwent surgery. The RDIs (DTX/CDDP/5-FU) were 0.90/0.83/0.90 in the D3PG group and 0.83/0.83/0.83 in the NPG group. Pts who achieved a pCR (D3PG/NPG) were 7/3 (22.6%/28.6%). The common grade ≥3 adverse events (D3PG/NPG) were neutropenia (12.5%/71.4%) and FN (6.3%/20.0%). Three-year relapse-free survival rate (D3PG/NPG) was 70.8%/54.4% (hazard ratio [HR] 0.525 [95% confidence interval (CI) 0.189-1.457], p=0.216). Three-year survival rate (D3PG/NPG) was 91.8%/70.5% (HR 0.497 [95%CI 0.104-2.35], p=0.378), respectively. Conclusions: The use of primary prophylactic PG on day 3 of preoperative DCF improved the safety and maintained the RDI in the D3PG group. The efficacy was comparable between the D3PG and NPG groups despite the higher number of pts with more advanced disease in the D3PG group.