Recent advances in novel drug delivery system aims at achieving better patient compliance. One of these advances is the formulation of orally dissolving tablets (ODTs) which dissolve instantaneously, releasing the drug, within a few seconds without the need of water. The main objective of this paper was to prepare and develop ODTs of Meclizine (MZ HCl) with sufficient mechanical integrity, content uniformity, and acceptable palatability to assist patients of any age for easy administration. Meclizine HCl is an anti-emetic drug used for management of dyspepsia, heartburn, epigastric pain, nausea, and vomiting. The interaction of meclizine and used excipients was studied using differential scanning calorimetry (DSC). The ODTs were prepared by direct compression method. The effect of varying concentrations of different superdisintegrants such as crospovidone, croscarmellose sodium, and sodium starch glycolate on disintegration time and dissolution rate was studied. The prepared tablets were evaluated for hardness, friability, disintegration time and in-vitro drug release. DSC studies revealed that no interaction between the drug and the used excipients. All tablets had hardness in the range 4.25.6 kp and friability less than 1%. Weight variation and drug content of all formulations were within official limit according to BP. In-vitro drug release study of ODTs tablets showed that more than 90% of the drug was released within 10 min. Palatability test by 12 volunteers showed acceptable taste and mouth feel. Thus, results obtained conclusively demonstrated successful rapid disintegration of the formulated tablets and acceptable palatability.