Methotrexate (MTX) is one of the most common anticancer drugs used for chemotherapy so far. However some problems such as high toxicity and short plasma half-life, have limited its use. To overcome these limitations, conjugation with polymers such as polyethylene glycol (PEG) is one the efficient approaches which has been attempted in recent years. The aim of the present study is to synthesize esters of MTX with PEGs of different molecular weights and to characterize their physicochemical properties. Polymeric esters (MTX-PEGs) of MTX with low, medium and high molecular weight PEGs (750 D, 5000 D and 35000 D, respectively) were synthesized using dicyclohexylcarbodiimide (DCC) as coupling agent and triethylamine (TEA) as catalyst. The purification was carried out using preparative TLC. Purified esters were characterized by UV, IR and (1)H-NMR spectroscopy methods and their thermal behavior was studied by differential scanning calorimetry (DSC). Also, an isocratic HPLC method with three mobile phase systems was set to determine the partition coefficient of the esters (log P). Gel permeation chromatography (GPC) was utilized for molecular weight determination of esters, which proved 1 : 1 conjugation of drug with each polymer. The stability and solubility of esters were determined in different pH values. The spectroscopy results indicated that esteric bond between MTX and PEGs were formed. The sharp endothermic peaks for MTX-PEGs were obtained in DSC which are similar to pure polymers, whilst a wide peak was observed for MTX. The values of log P for MTX-PEGs (+4.3, obtained by HPLC method) were remarkably different from log P of MTX (-1.4, obtained by shake-flask method). The stability results showed a pH range of 3-4 and an optimum polymer mw of 5000 for maximum stability of esters. A parabolic profile obtained from solubility studies that indicated the more solubility of MTX in alkaline condition (pH>5) and MTX-PEGs in acidic conditions (pH<5). Based on our results, it is concluded that MTX-PEGs were formed on an equimolar ratio of MTX and PEGs. The higher log P observed for the esters indicated dramatic physicochemical differences between MTX and its PEG conjugates and the higher stability and solubility in acidic medium showed a promising approach to improve the drug delivery of the conjugates, specially MTX-PEG5000 in the future.