An efficient and novel step-by-step synthesis of poly(amidoamine) (PAMAM) dendrimers by the divergent and method using ultrasound irradiation at room temperature is presented here. The results were compared with the conventional and microwave-assisted approach synthesis. The mass spectra analysis showed a major consumption of PAMAM G -0.5 (m/z 403.5) to obtain PAMAM G0, with an intensity below 10% by ultrasonic synthesis to difference of 30 and 50% of intensity in conventional and microwave synthesis, respectively. Also, a plausible mechanism is proposal in order to understand the byproducts formation in conventional and microwave synthesis, thus, the formation of defects occurs for PAMAM G0-arm cleave through of an alpha-beta breakdown of a betaine adduct generated in situ, decreasing the reaction yields.The structural analyses of the samples were carried out using FT-IR and NMR spectroscopic, and (ESI-MS) spectrometric analysis. The results showed that the ultrasound-assisted synthesis reduces the reaction time, prevents the formation of defective structures, and increases reaction yields.