Objective: Rizatriptan benzoate (RB) is a new generation anti-migraine drug. After oral administration, the peak plasma concentrations (t_max) occur in about 1 to 2.5 hrs depending on the formulation and the bioavailability which is about 40 to 45%. Food may delay the t_max by about 1 hour.  The aim of this work was to design and develop fast dissolving tablets of RB to improve the bioavailability and patient compliance applying the Mixture Experimental Design. Methods: Twenty formulations were prepared by direct compression each containing 14.53 mg of RB equivalent to 10 mg Rizatriptan with different proportions of superdisintegrants (X₁-X₃) according to the experimental design. The independent factors selected were the percentages of: Croscarmellose sodium (X₁), Explotab (X₂) and Polyplasdone XL 10 (X₃). The dependent variables investigated were: hardness (Y₁), disintegration time (Y₂) and cumulative % drug release after 10 minutes (Y₃). The formulations were evaluated for the pre-compression parameters to assess the powder compressibility and flowability (bulk and tapped density, Hausner's ratio, Carr's index and angle of repose) as well as the post-compression parameters (weight variation, friability, hardness, disintegration time, wetting time, water absorption ratio, drug content and in-vitro drug release). The optimized formulation was prepared and evaluated in the same manner. Results: All the evaluated parameters, either for powder blend or for the compressed tablets, were within the acceptable limits. The values of dependent variables ranged between 3.13-3.68 kg/cm²; 12.23-21.81 sec; and 94.44-99.83% for Y₁, Y₂ and Y₃ respectively. Polynomial regression equations for the variables (Y₁-Y₃) were generated and the quantitative effects of X₁-X₃ at different levels on Y₁-Y₃ could be predicted. Surface response and contour plots were plotted. The optimal ratios of different disintegrants were used to prepare the optimized formulation. The difference between the predicted and the observed data for the optimized formula were minimal. Conclusions: The use of direct compression technique and the mixture experimental design succeeded to produce fast dissolving tablets of RB with optimal hardness, minimal disintegration time and maximal in vitro drug release. The quantitative effects of the selected factors tested on the different variables were explored. Based on the obtained results, fast dissolving tablets of RB could be a potential dosage form for quick relieve of migraine patients.