Dengue virus serotypes 1, 2, 3, and 4 are transmitted by Aedes aegypti and Aedes albopictus mosquitoes, which cause illness in an estimated 100 million annually. Although dengue viruses are endemic throughout El Salvador, very little is known about their ecology and epidemiology. The principal methods to prevent and reduce dengue cases are through vector control and by adoption of a vaccine. In addition, understanding the environmental and socioeconomic factors associated with dengue could contribute to case reduction by targeting prevention efforts in dengue hotspots. This study investigated environmental and socioeconomic factors associated with dengue cases in El Salvador. Dengue cases were obtained from 2011 to 2013 for 262 municipalities. The mean incidence was determined for each municipality for the 3 year period. Negative binomial regression models evaluated the relationship between dengue cases and the environmental factors elevation, forest coverage, mean annual temperature, and cumulative precipitation. Twelve socioeconomic and infrastructure variables and their relationship with dengue were also investigated by using negative binomial regression. A total of 29,764 confirmed dengue cases were reported. The mean dengue incidence for 2011-2013 was 135/100,000. The highest number of dengue cases occurred in San Salvador and surrounding municipalities, as well as in two additional cities, Santa Ana and San Miguel; the highest incidence of dengue cases (per 100,000) occurred in cities in the west and at the center of the country. Significant environmental variables associated with dengue included temperature, precipitation, and non-forested area. The socioeconomic variables poverty rate, illiteracy rate, and school attendance, and the infrastructure variables percent of homes with sanitary service, municipal trash service, electricity, and cement brick flooring, as well as population density, were also significant predictors of dengue. Understanding these environmental and socioeconomic factors and their relationship with dengue will help design and implement timely prevention strategies and vector control to reduce dengue in El Salvador.