Relying on the most frequently reported barriers to adherence and convenient definitions of non-adherence may lead to less valid results. We used a dominance analysis (a regression-based approach) to identify the most important barriers to adherence based on effect size using data collected through an online survey. The survey included the Adherence Barrier Questionnaire, self-reported non-adherence defined as a 4-day treatment interruption, and HIV clinical outcomes. The sample (N = 1217) was largely male, gay identified, and White. Nearly 1 in 3 participants reported "simply forgot" as a barrier; however, in a dominance analysis, it yielded a small effect size it its association with a 4-day treatment interruption. Further, dominance analyses stratified by race/ethnicity and age suggested that not all barriers impact all groups equally. The most frequently reported barriers to adherence were not the most important, and interventions should focus on barriers more strongly linked to clinical outcomes.