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OBJECTIVE This paper aims to explore the effect of aspirin on the in-hospital mortality of patients with NVUGIB. METHODS An observational study retrospectively examined 1514 patients with NVUGIB based on a multi-center database. RESULT Our study reported a mortality rate of 4.8% in patients with NVUGIB, with 163 patients had a history of aspirin. Among 163 patients with an aspirin history, 76 patients (46.6%) continued to take aspirin in the hospital, with an average duration of 0.66 days after bleeding. Subsequent multivariate regression analysis showed heart rate (p <.001, OR = 0.978, 95%CI 0.969-0.987) and albumin (p =.019, OR = 0.658, 95%CI 0.464-0.933) were independent factors for aspirin-therapy after bleeding. Patients who received aspirin after NVUGIB (log-rank = 3.968, p =.046) had better survival than those who did not, but it was not an independent risk factor. The levels of albumin (p < .001, OR = 0.288, 95%CI 0.165-0.505) and INR (p =.013, OR = 1.166, 95%CI 1.033-1.316) and heart rate (p =.005, OR = 1.017, 95%CI 1.005-1.029) were independent factors of in-hospital mortality. CONCLUSIONS The independent risk factors for in-hospital mortality in patients with NVUGIB were albumin and INR and heart rate. The history of aspirin and the aspirin therapy after the bleeding did not affect the in-hospital mortality in patients with NVUGIB.