Organic MicroPollutants (OMPs) include a wide number of chemicals belonging to different classes, e.g. pharmaceuticals, drugs of abuse and their metabolites, steroids and hormones, endocrine-disrupting compounds (Barbosa et al. 2016; Chiavola et al. 2019). Increasing attention has been dedicated to OMPs, as a source of a high risk for public health and environment (Rodriguez-Narvaez et al. 2017). OMPs are characterized by low environmental concentrations (about ng L or μg L), high toxicity, very low biodegradability, and resistance to degradation in conventional treatments (Patel et al. 2019). The scientific community established that one of the main sources of release to the environment are the wastewater treatment plants (WWTPs), which are not specifically designed and operated to remove OMPs (Di Marcantonio et al., 2020; Luo et al., 2019). As it has been done to address other environmental problems, it is compulsory to determine the maximum permissible concentration on the basis of the acceptable risk for ecosystem and human health, as recommended by the new European Regulation on minimum requirements for water reuse 2020/741/EU. However, one limitation of the present EU approach is the focus on priority substances and on the risk associated with individual substances (Escher et al. 2018). Mixture risk assessment represents a breakthrough compared to European Environmental Quality Standard (EQS) of the European Water Framework Directive for surface water, since it allows to take into account potential synergism or antagonism which may cause adverse effects. The present study aims to compare the different Risk assessment methods. Specifically, the methods proposed by the European medicine agency for individual substances and the method for mixture of substances defined by Backhaus et al (2012) were applied. Moreover, the impact of the dilution factor (D) estimation, related to the flow rate of the receiving water bodies compared to the flow rate effluents from the WWTPs, was also assessed. The methods were applied to the concentrations of 3 illicit drugs, 6 pharmaceuticals and caffeine detected in different full-scale WWTPs in central Italy. The study highlighted that the individual risk for the monitored OMPs was always acceptable and considered medium only for Carbamazepine. In case of mixture of compounds, the risk was medium for the class of pharmaceuticals and low for the illicit drugs.