Pharmaceutical compounds can reach water bodies through sewage systems. The conventional process of water treatment is insufficient for the removal of these contaminants. The ozonation has great potential to be integrated into the physical-chemical treatment, since it promotes the reduction of pharmaceuticals, reduces the generation of disinfection byproducts and can reduce operational costs. In this work, the integration of the ozonation process with water treatment was studied. The ozone was applied in the pre-oxidation and intermediate ozonation stages, to evaluate the dependence of different variables. Water samples were collected from Arroio Diluvio, a river of the city of Porto Alegre (RS – Brazil). The doses of ozone were maintained between 0.5 and 1.0 mgO3 L−1 while the sulfate was varied between 25 and 150 mg·L−1. The pre-ozonation resulted in a removal of caffeine and ampicillin at pH 10.0, time of 15 min and coagulant concentration of 52.5 mg·L−1. The intermediate ozonation provided a removal of both pharmaceuticals, with pH 10.0 and a time of 5 min of bubbling. Based on the results, it was confirmed that the synergy of the ozonation process with conventional water treatment is an effective, sensitive and fast method for the removal of drugs from the aqueous medium.