Deer-vehicle collisions (DVCs) are a concern in the recovery of the endangered Florida Key deer (Odocoileus virginianus clavium) on Big Pine Key, Florida. Since the 1960s, nearly half of the total deer mortality has been attributed to DVCs; the majority of these mortalities occurring along the United States Highway 1 (US 1) corridor. In 2002, the Florida Department of Transportation completed modifications to a 2.6-km segment of the US 1 corridor that included fencing, experimental deer guards, and underpasses designed to prevent deer entry into the roadway and minimize DVCs. We evaluated the effectiveness of highway modifications in reducing Key deer-vehicle collisions pre- and post-project using long-term mortality data. Overall US 1 DVCs remained unchanged due to DVC increases along the unfenced section of US 1 on Big Pine Key; even though highway modifications (i.e., deer guards, fencing, and underpasses) reduced Key deer-vehicle collisions by 83–95 percent both post-project years. Experimental deer guards minimized deer crossings to six deer crossings the first post-project year and three crossings the second year. As a result, we recommend experimental deer guards in combination with fencing (and underpasses when applicable) can benefit wildlife in urban/suburban settings while maintaining human safety.