Objective To explore the vascular access infection (VAI) incidence of hemodialysis patients during the the maximum spread of the COVID-19 epidemic (epidemic period) compared with the corresponding period with no local cases of COVID-19 (control period). Methods A single-center, retrospective study was carried out. Adult patients who underwent hemodialysis at the Department of Blood Purification Center, the Affiliated Hospital of Xuzhou Medical University during the epidemic period between December 7, 2022 and February 23, 2023 and the control period between December 7, 2020 and February 23, 2021 were selected. The incidence of local access site infection (LASI) and access related bloodstream infection (ARBSI) in included patients were observed and compared. ResultsA total of 1 401 patients were included. Among them, there were 737 cases during the epidemic period and 664 cases during the control period. There was no statistically significant difference in the age, gender, and duration of catheterization among patients of different periods and pathway types (P>0.05). There was no statistically significant difference in the occurrence of LASI between the epidemic period and the control period (χ2=1.800, P=1.180). There was a statistically significant difference in the occurrence of ARBSI between the epidemic period and the control period [χ2=4.610, relative risk (RR)=2.575, 95% confidence interval (CI) (1.053, 6.298), P=0.032]. There was no statistically significant difference in the incidence of LASI and ARBSI at different stages in patients with arteriovenous fistula and unnel-cuffed catheters (TCC) (P＞0.05). There were statistically significant differences in the incidence of LASI [χ2=4.898, RR=3.832, 95%CI (1.058, 13.885), P=0.027] and ARBSI [χ2=7.150, RR=4.684, 95%CI (1.333, 16.460), P=0.005] among non cuffed catheters (NCC) patients at different stages. TCC patients might experience LASI (P<0.05) during the epidemic period and ARBSI (P<0.05) during the control period compared with the arteriovenous fistula patients; both central venous catheterization and NCC patients might experience LASI and ARBSI during the control period (P<0.05). Conclusion Targeting COVID-19 prevention may be associated with the reduction of vascular access infection in hemodialysis patients, in particular in NCC patients.