Background <p>Home-based dialysis, including peritoneal dialysis (PD) and home hemodialysis (HHD), has been suggested to reduce SARS-CoV-2 infection rates and improve outcomes compared to in-center dialysis, yet evidence from China remains scarce.</p> Objective <p>To investigate the risk and prognosis of Omicron infection among patients receiving home-based dialysis versus in-center dialysis during the Omicron surge in Shanghai, China.</p> Methods <p>This single-center retrospective cohort study included patients undergoing maintenance dialysis (home-based dialysis or in-center dialysis) at Ren Ji Hospital from December 1, 2022, to January 31, 2023. The primary endpoint was Omicron infection rate; secondary endpoints included infection timeline, all-cause mortality, and associated risk factors. Logistic regression was used to identify independent predictors.</p> Results <p>A total of 465 patients were included: 267 in the home-based dialysis group (263 PD, 4 HHD) and 198 in the in-center dialysis group. The infection rate was significantly lower in the home-based dialysis group than in the in-center dialysis group (52.1% vs. 88.4%, <i>P</i> &lt; .001). Home-based dialysis was an independent protective factor against infection. No significant difference was found in all-cause mortality between home-based dialysis and in-center dialysis groups (5.2% vs. 7.6%, <i>P</i> = .304). Advanced age, heart failure, and low serum albumin were associated with increased risk of death following infection.</p> Conclusions <p>Home-based dialysis significantly reduced the risk of Omicron infection without adversely affecting survival outcomes. Expanding home-based dialysis may have public health implications for dialysis care during future pandemics.</p>