ABSTRACT Annual influenza vaccination is recommended for patients with ESRD undergoing dialysis by the Advisory Committee on Immunization Practices (ACIP). Non-experimental studies suggest that inactivated, seasonal, standard-dose vaccines are not effective or minimally effective at reducing influenza-related hospitalizations or mortality in the dialysis population, and the high-dose vaccine provides little to no additional protection beyond the standard-dose vaccine for these outcomes. Two vaccine formulations using advanced technologies have been licensed in recent years. The adjuvanted influenza vaccine, licensed in 2015, enhances the magnitude of the immune response to vaccine antigens and broadens the response to include similar mismatched viruses through heterotypic protection. The recombinant influenza vaccine, licensed in 2013 (trivalent) and 2017 (quadrivalent), uses the baculovirus-insect cell system to produce recombinant influenza antigens. Evidence suggests that both the adjuvanted and recombinant influenza vaccines have higher vaccine effectiveness compared to standard-dose vaccines in the general population. Despite increasing uptake of the adjuvanted and recombinant influenza vaccines among the dialysis population in recent years, no large-scale studies have been conducted to evaluate the utilization, effectiveness, or safety of these newly licensed vaccines in the vulnerable population of patients on dialysis. A large study is needed to compare the newly licensed adjuvanted and recombinant vaccines versus other vaccines and to inform influenza prevention approaches in the dialysis population. We propose a large, non-experimental study using existing data from the United States Renal Data System (USRDS) to examine the use, effectiveness, and safety of various influenza vaccines among adult patients with ESRD undergoing dialysis. The large size of our study will allow us to characterize small differences in vaccine effectiveness and safety between adjuvanted or recombinant vaccines vs. standard or high-dose vaccines during the same influenza seasons. Vaccine effectiveness analyses will incorporate a broad range of influenza-related outcomes, including markers of severity of illness. Safety analyses will focus on a priori identified adverse events after influenza immunization. Study design and analyses will use robust methods to measure and account for confounding bias. Our findings will inform dialysis patients and their providers about the risks and benefits of different vaccines and influence vaccine policy, with the ultimate goal of reducing the burden of respiratory disease in this vulnerable population.