Safe reuse of wastewater requires high levels of pathogen inactivation. Ozone is a very effective disinfectant for viruses and has distinct benefits over other forms of disinfectants, in that it increases the clarity of water and can oxidize some chemical contaminants in water. However, because of the combination of high ozone demand of most wastewaters and rapid reaction with viruses, determination of ozone dose in wastewater and recycled water treatment is not well defined. While various surrogates are used as indicator organisms for human pathogenic viruses in water reuse practice, much less is known about the relationship between surrogates and human pathogenic viruses for ozone disinfection in wastewater. In this study, the ozone inactivation dose response of several surrogates (Escherichia coli, coliphage T1, T4, PRD-1, FX174, and MS2) and human pathogenic viruses (poliovirus 1, echovirus 11, coxsackievirus B5, and adenovirus 2) were compared for the first time in secondary effluent wastewater. A unique reduction equivalent dose method was proposed to compare the inactivation of the microorganisms studied across waters with varying ozone demand. Inactivation of all viruses and surrogates studied was greater than 4 log at ozone Ct levels of less than 1 (mg/L)-min. E. coli and PRD-1 were identified as conservative surrogates for indicating inactivation of human pathogenic viruses in ozone disinfection of wastewater, providing a tool for practitioners and regulators to confidently accept ozonation systems for virus inactivation in wastewater reuse.