Knowledge of the effects of ionic strength (IS) on the transport and retention of polyacrylamide microspheres in porous media is essential for their application in reservoir water shutoff treatment, especially under high-IS conditions. In this work, retention and release experiments were conducted in a transparent sand-packed micromodel at various IS values from 0.001 to 0.20 M to investigate the pore-scale transportretentionrelease processes of polyacrylamide microspheres, as well as their retention mechanisms and spatial distributions in porous media. DLVO interaction profiles, chamber dissections, and mass-balance calculations were used to quantitatively analyze the effects of IS on the transport and retention of polyacrylamide microspheres during reservoir water shutoff treatment. The results indicated that the retention of polyacrylamide microspheres increased with IS because of the diminution/elimination of the energy barrier at high IS levels. Straining at pore throats was the largest contributor to the retention of polyacrylamide microspheres for all IS conditions. IS reduction was beneficial to the release of polyacrylamide microspheres that were loosely retained on sand grain surfaces by secondary energy minima. Nevertheless, most of the released polyacrylamide microspheres were once again retained by straining, which would further enhance the water shutoff performance. Irreversible retention by primary energy minima ranged between 0.37% and 4.65% with increasing IS, and the elimination of the energy barrier under high-IS conditions could enhance this process.