INTRODUCTION: This study aimed to evaluate both the clinical efficacy and safety of airway stent placement in in the treatment of patients with esophageal cancer-associated airway esophageal fistula (AEF). The focus is on evaluating improvements in patient survival and quality of life. METHODS: Overall, this study enrolled 111 patients diagnosed with esophageal cancer-associated AEF. Among them, 50 (45.0%) and 61 (55.0%) patients received airway stent placement and conservative treatment, respectively. Follow-up assessments were conducted to determine the clinical efficacy and safety of the interventions, with survival and quality of life as the primary endpoints. RESULTS: By the end of the follow-up, 98 of 111 patients (88.3%) had died, leaving 13 survivors (11.7%). Patients with esophageal cancer-associated AEF had an overall mean survival time of 147.4 (95%CI, 123.9-170.9) days. Patients in the stent placement group had a mean survival of 192.5 (95% CI, 151.2-233.7) days, which was significantly longer than the 110.0 (95% CI, 88.1-131.8) days in the conservative treatment group (p <
0.001). Sex (p = 0.017), tumor stage (p = 0.030), surgery (p = 0.005), pulmonary infection (p <
0.001), fistula size (p <
0.001), and pre-Karnofsky Performance Status (KPS) (p <
0.001) were the independent risk factors affecting survival. Furthermore, patients in the stent placement group demonstrated improved KPS scores post-treatment, increasing from 48.2 to 57.9 (p = 0.017). CONCLUSION: Airway stent placement is beneficial in alleviating the symptoms, quality of life, and survival of patients with esophageal cancer-associated AEF.