The production of biodiesel from waste cooking oil (WCO) has been studied by transesterification reaction in an agitated reactor. An alternative to decrease heating and reaction time is to use a hydrodynamic cavitation reactor. The objective of this work was to evaluate biodiesel production in a hydrodynamic cavitation reactor using WCO. A response surface methodology (RSM) was used to find the best experimental conditions. Yield and energy consumed per kilogram of biodiesel produced (ECPKB) surfaces were adjusted. The independent variables were: the methanol-oil molar ratio (6:1 - 5:1 - 4:1) and the percentage of potassium hydroxide catalyst (1% and 0.5%). The flow rate, temperature, electrical energy consumed, and reactor inlet and outlet pressures were monitored. According to the RSM, the optimum production parameters were: molar ratio (MR) 4:1 and 0.5% potassium hydroxide catalyst percentage (KOH). The biodiesel produced was analyzed by a gas chromatography, a cetane index and heat value laboratory tests according to ASTM D6751 standard. Due to high content of methyl esters (above 98%) for 5:1 MR and 0.5% KOH these conditions were selected as the best for production. These conditions led to the highest yield of 1.07 and 74.07 kJ/kg of ECPKB. The reaction time was less than 10 minutes for all conditions, indicating a breakthrough for biodiesel production.