The primary objective of this investigation was to improve the oral bioavailability of a selected poorly water-soluble drug tacrolimus by developing Liquisolid (LS) compacted tablets. LS compact formulations were prepared using 3 different non-volatile solvents PEG600, Capryol 90 and labrasol. Neusillin US2 and aerosil were used on the porous carrier and coating material respectively for all nine formulations. The selected LS3, LS 5, and LS 9 were compressed into tablets using cross carmellose sodium as disintegrants. The formulations were evaluated for content uniformity, friability, hardness, disintegration test, in vitro drug release studies, and in vivo pharmacokinetic studies. The drug-excipient compatibility study by FTIR and DSC investigation revealed no potential interaction. The optimized formulation LS3 exhibited an improved dissolution rate with disintegration in less than 10 min. Pharmacokinetic study for the optimized liquisolid formulation LS3 exhibited 5 folds improvement in oral bioavailability.