Objective: The objective of this study was to design, evaluate and optimize effervescent tablets containingbismuth sub-citrate with sufficient hardness and friability in treatment of peptic ulcer. Materials and Methods: Effervescent tablets were prepared by direct compression method and were optimized using irregular factorial design. Amount of citric acid, sodium bicarbonate to citric acid molar ratio, polyvinyl pyrrolidone K 30 (PVP k30), polyethylene glycol 6000 (PEG 6000) were selected as independentvariables, whereas disintegration time, amount of carbon dioxide (CO2 ), friability, pH, and hardness were selected as dependent variables. All the batches were assessed for various pre and post compression characteristics such as flowability, hardness, friability, effervescent time, pH, and content uniformity. For the enhancement of tablets’ palatability, the components of optimized formulation were mixed with same amounts of different flavoring agents. Results: The best results obtained from effervescent tablets preparedby 500 mg citric acid, 5% PEG 6000 and 3% PVP k30 while the molar ratio of the sodium bicarbonate to citric acid was 3. The disintegration time, amount of CO2, friability, pH, and hardness of optimized formulation were confirmed to be 95. 33 ± 1. 15 sec, 398. 73 ± 1. 46 mg, 0. 73%, 6. 0 ± 0. 06 and 72. 3 ± 5. 5 N, respectively. The most pleasant taste according to volunteers’ acceptability was the taste of cherry. Conclusion: These results suggest that developed effervescent tablets may be promising for delivery of bismuth sub-citrate in peptic ulcers therapy.