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Surface waters used for drinking water supply often receive upstream wastewater effluent inputs, resulting in de facto wastewater reuse for drinking water and recreation. As populations grow, demands on water supplies increase. As this trend continues, it creates the need to understand the risks associated with such reuse. In North Carolina, potable reuse has been proposed as a combination of at least 80% surface water with up to 20% tertiary-treated, dual-disinfected, reclaimed wastewater, which is then stored for 5 days and further treated using conventional drinking water treatment methods. The state of North Carolina has set standards for both intake surface water and for the reclaimed water produced by wastewater utilities, using indicator microorganisms to measure compliance. The goal of this study was to quantify fecal indicator microorganisms, specifically E. coli, coliphages, and C. perfringens as well as key pathogens, specifically Salmonella spp. bacteria, adenoviruses, noroviruses, and the protozoan parasites Cryptosporidium and Giardia, in two types of water representing potential candidates for potable reuse in North Carolina, (1) run of river surface water and (2) sewage-impacted surface waters, with the purpose of determining if there are predictive relationships between these two microorganism groups that support microbial indicator reliability.