Research suggests gender differences exist in achieving undetectable viral load (UVL) among persons living with HIV (PLHIV), and that psychosocial health factors may play a role. The present study examined these factors among African-American PLHIV enrolled in the BEACON study. Participants completed self-report surveys and gave biomarker data. Poisson regression with robust standard errors was implemented. Men with moderate religious activity had 1.3 times the likelihood of UVL as men with low religious activity (p < 0.10; N = 199). Men with 1–2 mental illness diagnoses had 1.3 times the likelihood of UVL as men with none (p < 0.05). Women using 1–2 substances had 28 % lower likelihood of UVL than non-using women (N = 122; p < 0.10). Finally, women with frequent doctor-patient communication had 35 % higher likelihood of UVL as women with less doctor-patient communication (p < 0.05). Results suggest that social support, substance use, and mental illness function differently among men and women. Healthcare professionals should employ gender-specific interventions to address and improve HIV health outcomes.