Barriers to retention in HIV care are detrimental to patients’ progress along the HIV continuum of care. Previous literature has focused on individual, client-level barriers and interventions to address them. In contrast, less work has examined the role of system-level barriers on HIV care outcomes. The present study seeks to understand how individual and systemic barriers individually are associated with clinic appointment attendance and virologic suppression in HIV-infected patients attending the largest HIV clinic in Miami-Dade, Florida. In addition, we examined the synergistic effects of these barriers as potential syndemic factors on these health outcomes. Barriers to clinic attendance were determined in a face-to-face study interview with 444 HIV-infected outpatients (187 regular attenders, 191 irregular attenders, 66 non-attenders) identified from electronic medical records. Compared to the other attendance groups, non-attenders had higher viral loads, were less likely to be virologically suppressed, had lower CD4 counts, had higher depressive symptoms, life chaos, lower quality of life, and higher rates of food insecurity and recent drug use. Additionally, non-attenders compared to regular attenders had lower physician relationship ratings, had lower medical information clarity, and more often reported transportation as a barrier to clinic attendance. When viewed as a syndemic, compared to patients not reporting any barriers, patients with three or more individual-level barriers were more likely to have a detectable viral load (OR = 3.60, 95%CI [1.71, 7.61]). Our findings suggest that patients presenting to the clinic with multiple barriers should be prioritized for assistance and future interventions to improve retention in care. Interventions should address multiple individual and system level barriers simultaneously with particular attention to addressing depressive symptoms, organizational skills, relationship with the physician, and HIV-related health education.