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Pharmaceuticals are often found in the water environment and are not completely degraded by conventional treatment processes. There are some techniques, such as advanced oxidative processes (AOPs), which can promote, in addition to the total removal of contaminants, their mineralization, transforming them into CO2 and water. Thus, the objective of this work was to evaluate the mineralization capacity of the emerging pollutants caffeine and ampicillin, present in a real aqueous matrix, through ozonation. Factorial planning was carried out by Central Composite Design (CCD) under the Response Surface Methodology (RSM). Water samples were collected from Arroio Dilúvio, a river that cuts through the city of Porto Alegre (RS -- Brazil), which receives domestic, hospital, and industrial effluents in nature. The experiments were conducted from the analysis of the influence of pH, time, and ozone flow rate variables. The ozonation system consisted of an oxygen concentrator, an ozone generator, and a gas washer bottle. With removals of caffeine and ampicillin around 100 and 99.7%, respectively, a mineralization of 30.8% was also obtained under conditions of pH 8, with an applied ozone dosage of 830 mg.L-1. In this process, the gas phase concentration was at 16.7 mg.L-1 when applied to 200 mL sample for 10 minutes and ozone flow rate of 1 L.min-1. A linear relationship was observed between the real and predicted values, and it has been shown that the relationship of the residual plot confirmed a sufficient approximation of the method for the optimization process. Finally, the desirability function showed adequate operating conditions for the mineralization of compounds by ozonation. Therefore, it is considered that this technique is effective for the mineralization of the pharmaceuticals studied, and can be applied as a way of treating a contaminated real matrix. [ABSTRACT FROM AUTHOR]