Research demonstrates that homelessness is associated with frequent use of emergency department (ED) services, yet prior studies have not adequately examined the relationship between frequent ED use and utilization of non-ED health care services among those experiencing homelessness. There has also been little effort to assess heterogeneity among homeless individuals who make frequent use of ED services. To address these gaps, the present study used Medicaid claims data from 2010 to estimate the association between the number of ED visits and non-ED health care costs for a cohort of 6,338 Boston Health Care for the Homeless Program patients, and to identify distinct subgroups of persons in this cohort who made frequent use of ED services based on their clinical and demographic characteristics. A series of gamma regression models found more frequent ED use to be associated with higher non-ED costs, even after adjusting for demographic and clinical characteristics. Latent class analysis was used to examine heterogeneity among frequent ED users, and the results identified 6 characteristically distinct subgroups among these persons. The subgroup of persons with trimorbid illness had non-ED costs that far exceeded members of all 5 other subgroups. Study findings reinforce the connection between frequent ED use and high health care costs among homeless individuals and suggest that different groups of homeless frequent ED users may benefit from interventions that vary in terms of their composition and intensity.