A straightforward aqueous-mediated ultrasound-promoted novel protocol is developed for the quantitative synthesis of medicinally important spiro[indole-thiazolidinone] libraries by the tandem reaction of readily available reagents using cetyltrimethylammonium bromide as a phase transfer catalyst. The present method is more convenient and efficient as compared to multistep conventional processes and it obviates the azeotropical removal of water and use of carcinogenic solvents and dehydrating agents. Other features of this method are operational simplicity and increased safety for high speed synthesis and minimal environment impact.