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Objective: The aim of this study was to develop and optimize the formulation of tablets containing Aquilaria crassna extract using the direct compression method. Methods: D-optimal design based on three independent variables was applied to evaluate the cause-effect relations and optimize the A. crassna tablet formulation. The weight variation (Y 1 ), disintegration time (Y 2 ), hardness (Y 3 ) and friability (Y 4 ) were investigated with respect to three independent variables including % dicalcium phosphate anhydrous (DCPA) in filler (X 1 ), % filler (X 2 ) and % croscarmellose sodium (CCNa) (X 3 ). The dissolution study of the optimized A. crassna tablets were investigated in simulated gastric fluid (SGF) (pH 1.2) using a validated high-performance liquid chromatography (HPLC) method for mangiferin analysis. Results: All investigation factors were found to have significant effects on the physical properties of A. crassna tablet. The tablet hardness and the disintegration time increased in positive relations with the ratios of DCPA. The results exhibited the negative relations between disintegration time and the percentages of CCNa. The optimized A. crassna tablet formulation which included 35 % (w/w) DCPA in filler, 60 % (w/w) filler and 7% (w/w) CCNa possessed the weight variation of 1.38 % (w/w), the disintegration time of 6.29 min, the hardness of 85.63 N and the friability of 0.41 % (w/w). The optimized A. crassna tablet formulation was experimentally examined which demonstrated a good agreement between the experimental and predicted values. Mangiferin was found to release completely from the optimized A. crassna tablets within 30 min. Conclusion: The cause-effect relations and optimization of A. crassna tablet formulation were investigated and reported for the first time. The A. crassna spray-dried extract could be formulated into tablet by direct compression method with good mechanical properties and acceptable release profile.