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Objective. The Centers for Disease Control and Prevention has recommended emergency department (ED) opt-out HIV screening since 2006. Routine screening can prove challenging due to the ED's complexity and competing priorities. This study examined the implementation and evolution of a routine, integrated, opt-out HIV screening program at an urban academic ED in Alabama since August 2011. Methods. ED routine, opt-out HIV screening was implemented as a standard of care in September 2011. To describe the outcomes and escalation of the screening program, data analyses were performed from three separate data queries: ( 1) encounter-level HIV screening questionnaire and test results from September 21, 2011, through December 31, 2013; ( 2) test-level, fourth-generation HIV results from July 9 through December 31, 2013; and ( 3) daily HIV testing rates and trends from September 9, 2011, through June 30, 2014. Results. Of the 46,385 HIV screening tests performed, 252 (0.5%) were confirmed to be positive. Acute HIV infection accounted for 11.8% of all HIV patients identified using the fourth-generation HIV screening assay. Seventy-six percent of confirmed HIV-positive patients had successful linkage to care. Implementation of fourth-generation HIV instrument-based testing resulted in a 15.0% decline in weekly HIV testing rates. Displacement of nursing provider HIV test offers from triage to the bedside resulted in a 31.6% decline in weekly HIV testing rates. Conclusion. This program demonstrated the capacity for high-volume, routine, opt-out HIV screening. Evolving ED challenges require program monitoring and adaptation to sustain scalable HIV screening in EDs.