Abstract: Levofloxacin is a broad spectrum synthetic fluoroquinolone antibiotic and is used to treat infections including: respiratory tract infections, cellulites urinary tract infections, prostatis, endocarditis, meningitis, pelvic inflammatory disease, traveler's diarrhea, tuberculosis and plague. Levofloxacin is the S-enantiomer of a racemate, named ofloxacin.Many synthetic routes for preparing levofloxacin have been reported. Most of them involved using non-feasible reagents, high temperature during synthesis, non-recyclable, costly and poisonous solvents. Therefore, the selection of an inexpensive, recoverable and non-toxic medium for synthesis with high yield and also having minimum negative effect on the environment is of prime importance in industrial scale. Levofloxacin is produced by the reaction of (S)-(-)-9, 10-difluoro-3-methyl-7oxo-2, 3-dihydro7H-pyrido [1, 2, 3-de] [1, 4] benzoxazine-6-carboxylic acid with N-methyl piperazine in a polar solvent, preferably at a technically acceptable temperature to form levofloxacin in an industrially feasible yield. The pure levofloxacin is used as hemihydrates, which has the empirical formula of C₁₈H₂₀FN₃O₄ ½ H2O.Herein, we wish to investigate the effect of various solvent systems on the yield of reaction. Depends on the solvent to be used, different temperature and reaction time for synthesis is considered. The best solvent will be selected based on the comparison of the measured yields and also the ability of recovering it in order to use for next batches. Another aspect of the present research is to develop an efficient method for purification of crude levofloxacin and convert it to hemihydrates form, which is stable and can be used as an API (Active Pharmaceutical Ingredient). The selection of solvent and also the amount of water to be used in purification step in order to change crystalline structure is very important, which will be investigated in this section. The results show that using DMSO for synthesis and Ethanol/Water for purification step are the best choices.