Ruggedness tests were performed for the high-performance liquid chromatographic method for the determination of tetracycline hydrochloride from the United States Pharmacopeia XXII using Plackett-Burman and fractional factorial designs. Different statistical interpretation criteria for both kinds of designs were compared. The interpretation criteria for the Plackett-Burman designs were based on the use of dummy factors in the design and for the fractional factorial designs on two-factor interaction effects. The statistical interpretation criteria were compared with graphical ones (e.g., normal probability plots). The results of the designs (the ruggedness tests) were interpreted based on the above criteria. Other potential alternatives for statistical interpretation were also examined. Two different types of stationary phases (C 8 and C 1 8 ) were tested and compared.