The aim of the current study was to investigate the impact of early oral feeding (EOF) on inflammatory cytokine levels after McKeown minimally invasive esophagectomy (MIE) for cancer. This study was based on a randomized controlled trial (NCT01998230). Patients with esophageal cancer who received McKeown MIE were randomly allocated into a group that started oral feeding on postoperative day (POD) 1 (EOF group) or a second group that received nil by mouth until 7 days after operation (late oral feeding [LOF] group). We chose 86 patients, 46 patients in the EOF group and 40 patients in the LOF group, in which to analyze inflammatory cytokine levels (interleukin [IL]-6, IL-8, tumor necrosis factor-a [TNF-α], and monocyte chemotactic protein-1 [MCP-1]). The EOF and LOF groups exhibited similar preoperative IL-6, IL-8 TNF-α, and MCP-1 levels. The levels of the four inflammatory cytokines at PODs 1 and 3 weresignificantly higher than the preoperative levels (all p<0.001). At POD 5 the levels of all four inflammatory cytokines were decreased compared with those at PODs 1 and 3. At PODs 3and 5 the levels of IL-6, IL-8, and TNF-α were significantly lower in the EOF group than in the LOF group (all p < 0.05). AtPOD 3 the MCP-1 levels in the EOF group were significantly lower than those in the LOF group (all p < 0.05). Compared with conventional rehabilitation programs the EOF protocol may decrease stress response after McKeown MIE.