Objective: To characterize the epidemiology and transmitted drug resistance mutation (TDRM) patterns among individuals with newly diagnosed HIV-1 infection seen at Henry Ford Hospital in Detroit from 2006 to 2008. Methods: This was a retrospective analysis of medical records from individuals aged ≥18 years with a new diagnosis of HIV-1 infection. Individuals who underwent genotypic resistance testing were included in the study. Results: One hundred thirty-three individuals were included; 99 (74%) were males, 104 (78%) were African-Americans, and 61 (46%) had a CD4+ count of ≤200 cells/μl. The prevalence of TDRM was 17% (23/133). Non-nucleoside reverse transcriptase mutations occurred in 11 (8%), nucleoside reverse transcriptase mutations in 13 (10%), and protease inhibitor mutations in 10 (8%). CD4+ count >350 cells/μl and HIV viral load on presentation were associated with TDRM in the multivariate analysis (p=0.004 and p<0.001 respectively). Conclusions: Late diagnosis of HIV-1 and transmitted antiretroviral resistance are relatively common in Detroit. While most newly diagnosed persons were candidates for antiretroviral therapy on presentation, the high prevalence of TDRM has significant implications in the selection of first-line highly active antiretroviral therapy (HAART). © 2011 International Society for Infectious Diseases.