We have synthesized various types of poly(ethylene glycol) (PEG)-ibuprofen conjugates by nucleophilic substitution of bromo-terminated PEG with ibuprofen-Cs salt. The conversion of the terminal hydroxyl groups to bromo-termini was quantitative, as was the drug conjugation process, which suggests that the present synthetic method is very useful for the preparation of PEG-based prodrugs from pharmaceuticals having carboxyl functionalities. The drug-release behavior of the prodrugs was examined in both phosphate buffer (PBS, pH 7.4) and rat plasma. From the drug-release behavior in PBS, we determined that each prodrug has high storage stability. The drug-release rate was observed to be much faster in rat plasma than in buffer solution as a result of the acceleration effect provided by enzymes present in the plasma. The drug-release rate in rat plasma depends on the degree of molecular aggregation of the prodrugs, which can be changed effectively by the nature of their spacer groups or by the use of Pluronic as the polymer carrier.