Many organic micropollutants present in wastewater, such as pharmaceuticals and pesticides, are poorly removed in conventional wastewater treatment plants (WWTPs). To reduce the release of these substances into the aquatic environment, advanced wastewater treatments are necessary. In this context, two large-scale pilot advanced treatments were tested in parallel over more than one year at the municipal WWTP of Lausanne, Switzerland. The treatments were: i) oxidation by ozone followed by sand filtration (SF) and ii) powdered activated carbon (PAC) adsorption followed by either ultrafiltration (UF) or sand filtration. More than 70 potentially problematic substances (pharmaceuticals, pesticides, endocrine disruptors, drug metabolites and other common chemicals) were regularly measured at different stages of treatment. Additionally, several ecotoxicological tests such as the Yeast Estrogen Screen, a combined algae bioassay and a fish early life stage test were performed to evaluate effluent toxicity. Both treatments significantly improved the effluent quality. Micropollutants were removed on average over 80% compared with raw wastewater, with an average ozone dose of 5.7 mg O3 l−1 or a PAC dose between 10 and 20 mg l−1. Depending on the chemical properties of the substances (presence of electron-rich moieties, charge and hydrophobicity), either ozone or PAC performed better. Both advanced treatments led to a clear reduction in toxicity of the effluents, with PAC-UF performing slightly better overall. As both treatments had, on average, relatively similar efficiency, further criteria relevant to their implementation were considered, including local constraints (e.g., safety, sludge disposal, disinfection), operational feasibility and cost. For sensitive receiving waters (drinking water resources or recreational waters), the PAC-UF treatment, despite its current higher cost, was considered to be the most suitable option, enabling good removal of most micropollutants and macropollutants without forming problematic by-products, the strongest decrease in toxicity and a total disinfection of the effluent.