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The delivery of high-quality HIV care in rural settings is a global challenge. Despite the successful expansion of antiretroviral therapy (ART) in Africa, viral load (VL) monitoring and ART adherence are poor, especially in rural communities. This article describes a case study of an ART program in the deeply rural Eastern Cape of South Africa. The Zithulele ART Program initiated five innovations over time: (1) establishing district hospital as the logistical hub for all ART care in a rural district, (2) primary care clinic delivery of prepackaged ART and chronic medications for people living with HIV (PLH), (3) establishing central record keeping, (4) incentivizing VL monitoring, and (5) providing hospital-based outpatient care for complex cases. Using a pharmacy database, on-time VL monitoring and viral suppression were evaluated for 882 PLH initiating ART in the Zithulele catchment area in 2013. Among PLH initiating ART, 12.5% (n = 110) were lost to follow-up, 7.7% (n = 68) transferred out of the region, 10.2% (n = 90) left the program and came back at a later date, and 4.0% (n = 35) died. Of the on-treatment population, 82.9% (n = 480/579) had VL testing within 7 months and 92.6% (n = 536/579) by 1 year. Viral suppression was achieved in 85.2% of those tested (n = 457/536), or 78.9% (n = 457/579) overall. The program's VL testing and suppression rates appear about twice as high as national data and data from other rural centers in South Africa, despite fewer resources than other programs. Simple system innovations can ensure high rates of VL testing and suppression, even in rural health facilities. [ABSTRACT FROM AUTHOR]