The disparity in viral suppression rates between Latino and non-Latino White patients in HIV care appears to be narrowing, but it is unclear if depression and substance use perpetuate this disparity. We analyzed electronic medical records from the CFAR network of integrated clinical systems cohort. First observations/enrollment data collected between 2007 and 2013 were analyzed, which included survey (race/ethnicity, depression, substance use, adherence) and clinical data (viral suppression). We estimated indirect effects with a regression-based bootstrapping method. In 3129 observations, Latinos and non-Latino Whites did not differ in depression or alcohol use (ORs 1.11, 0.99, ns), but did in drug use (OR 1.13, p < .001). For all patients, depression and substance use were indirectly associated with small increases (ORs 1.02-1.66) in the odds for a detectable viral load, via worse adherence. We conclude that variables not captured in EMR systems (e.g., health literacy, structural factors) may better explain viral suppression disparities that persist.