BACKGROUND/AIM: To evaluate the impact of prophylactic administration of pegfilgrastim in esophageal cancer (EC) patients treated with chemotherapy consisted of docetaxel, cisplatin, and fluorouracil (DCF). PATIENTS AND METHODS: Among 102 patients who received neoadjuvant or induction DCF for primary advanced EC, 65 received prophylactic pegfilgrastim and 37 did not. The association of pegfilgrastim with adverse events and clinicopathological outcomes was retrospectively analyzed. RESULTS: In the pegfilgrastim group, the incidence of grade >3 neutropenia was lower (30.8% vs. 62.2%) and more patients avoided dose reduction or discontinuation of chemotherapy (32.3% vs. 70.3%). The radiological (PR≤) and histopathological (grade 1b≤) response rates were significantly higher (69.2% vs. 43.2% and 59.2% vs. 35.7%). Three-year overall survival and progression-free survival rates were significantly higher (65.0% vs. 48.6%, p=0.033; 56.1% vs. 35.1%, p=0.007, respectively). CONCLUSION: Prophylactic pegfilgrastim in DCF may relieve adverse events and improve the oncologic outcome of EC patients.