Intervention studies with vulnerable groups in the emergency department (ED) suffer from lower quality and an absence of administrative health data. We used administrative health data to identify and describe people experiencing homelessness who access EDs, characterize patterns of ED use relative to the general population, and apply findings to inform the design of a peer support program. We conducted a serial cross-sectional study using administrative health data to examine ED use by people experiencing homelessness and nonhomeless individuals in the Niagara region of Ontario, Canada from April 1, 2010 to March 31, 2018. Outcomes included number of visits; unique patients; group proportions of Canadian Triage and Acuity Scale (CTAS) scores; time spent in emergency; and time to see an MD. Descriptive statistics were generated with t tests for point estimates and a Mann-Whitney U test for distributional measures. We included 1,486,699 ED visits. The number of unique people experiencing homelessness ranged from 91 in 2010 to 344 in 2017, trending higher over the study period compared with nonhomeless patients. Rate of visits increased from 1.7 to 2.8 per person. People experiencing homelessness presented later with higher overall acuity compared with the general population. Time in the ED and time to see an MD were greater among people experiencing homelessness. People experiencing homelessness demonstrate increasing visits, worse health, and longer time in the ED when compared with the general population, which may be a burden on both patients and the health care system.