A new, fast and efficient method was developed for the separation and simultaneous quantification of acesulfame-K, aspartame, cyclamate, neotame and saccharin in food by ultraperformance liquid chromatography (UPLC) and diode array detector (DAD). Univariate strategies were applied for the optimisation of mobile phase pH, proportion of solvents in the mobile phase, flow rate and column temperature. Multivariate techniques were used for the simultaneous optimisation of 13 responses applying the Derringer and Suich desirability function. Many of the models presented lack of fit. However, it was possible to optimise the method using strategies for the restriction of the region to be investigated by the algorithm used in the desirability function. The optimised method was validated and applied to nine food matrices (soft drink, nectar, juice, ready-todrink tea, jam, barbecue sauce, tomato sauce, instant juice and instant pudding), presenting good resolution, rapid analysis (11 min) and low use of reagents. This indicates that the UPLC is an excellent alternative for the simultaneous analysis of artificial sweeteners in foods.