Objectives: This community-based study explores the syndemic nature of HIV/AIDS risk and resilience among Indigenous Kichwa communities in the province of Imbabura, Ecuador. This study elucidates individual and community-level factors that serve to exacerbate HIV/AIDS risk, as they relate to underlying macrolevel, structural forces. Critically, this study also elicited opportunities for community-based opportunities for resiliency from HIV/AIDS. Study design: Exploratory qualitative study. Methods: Guided by syndemic theory, a qualitative study was conducted to explore HIV risk and resilience among Indigenous Kichwa communities in the Northern Andean highlands of Ecuador. Eight focus groups (n = 59) with men and women from two communities were conducted. The data were analyzed using applied thematic analysis techniques. Results: Identified risk factors for HIV/AIDS centered around the following themes: (1) parents leaving the community for work, (2) alcohol and drug consumption, (3) unprotected sex, and (4) barriers to health care. Identified HIV/AIDS resiliency factors included the preservation of Indigenous culture and family-focused interventions. Conclusions: The identified risk factors for HIV/AIDS are interrelated within a complex syndemic relationship. The mutually reinforcing individual-level risk factors of substance abuse and risky sexual behavior coalesce with violence to exacerbate the risk for HIV/AIDS acquisition among Ecuadorian Highland Indigenous communities. Moreover, HIV/AIDS risk prevails in the macrolevel context of disproportionate unemployment among Indigenous peoples and a systematically fragmented healthcare system. It is critical that public health professionals work to revolutionize the systematic discrimination that underpins indigenous health disparities at-large.