The best demonstration of the ruggedness of a method is monitoring its performance on an ongoing basis as part of the analytical quality control applied in the laboratory. However, an initial demonstration of the ruggedness is often performed as one aspect of the method validation, to give confidence that the method should perform well under normal variations in conditions in routine application. This initial ruggedness testing is typically performed using either multiple replicate analyses or application of design of experiments (DoEs) which minimizes the number of analyses, time and effort required to detect influences on the measurement results. Two DoEs were applied for ruggedness testing for a modified QuEChERS multiresidue method for the detection of pesticide residues in potato by GC–MS/MS. Seven experimental factors were studied using an eight-run Plackett–Burman design replicated three times and an augmented definitive screening design with 34 runs. The relative effectiveness of the two approaches is discussed, in terms of their statistical significance, their cost-effectiveness and the richness of information they provide on the effects of the parameters investigated and the actual robustness of the method being tested.