ObjectiveTo investigate the short-term outcomes and quality of life (QoL) in patients undergoing minimally invasive McKeown esophagectomy with the assistance of near-infrared fluorescence imaging (NIRF). MethodsThis retrospective study included consecutive patients who underwent minimally invasive McKeown esophagectomy performed by a single surgical team at the Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, between July 2020 and December 2023. Patients were divided into two groups based on whether NIRF was used to assess gastric conduit perfusion: the NIRF group and the control group. Clinical characteristics, perioperative data, major postoperative complications, and short-term QoL were compared between the two groups. ResultsA total of 246 patients were included. The NIRF group comprised 132 patients, including 85 males and 47 females with a mean age of (62.6±6.7) years, and the control group consisted of 114 patients, including 78 males and 36 females with a mean age of (64.4±3.8) years. No significant differences were observed between the two groups in terms of operative time, intraoperative blood loss, number of dissected lymph nodes, or length of hospital stay (all P>0.05). There were also no significant differences in the rates of recurrent laryngeal nerve injury, cardiopulmonary complications, chylothorax, and 90-day mortality (all P>0.05). The incidence of anastomotic leakage was 3.7% in the NIRF group, lower than the 7.8% in the control group. Receiver operating characteristic (ROC) curve analysis, generated from software-assisted fluorescence intensity data, indicated that maximum fluorescence intensity (MFI) was associated with gastric conduit perfusion. An MFI of 20.5 was determined as the optimal cut-off value for predicting anastomotic leakage (P<0.05). Further analysis within the NIRF group showed that a fluorescence appearance time >95 s and a flow velocity <1.7 cm/s were significantly associated with an increased risk of anastomotic leakage (P<0.05). Regarding QoL, the SF-36 scores at 3 months postoperatively were significantly better in the NIRF group than in the control group (P<0.05). However, no significant difference was observed between the two groups at 12 months postoperatively (P>0.05). Conclusion The use of NIRF during minimally invasive esophagectomy provides an effective method for assessing gastric conduit perfusion via quantitative parameters. It significantly reduces the incidence of anastomotic leakage, thereby accelerating early postoperative recovery and improving short-term QoL.