Heat-and salt-resistant amphiprotic polyacrylamide microsphere (APMS) was synthesized using inverse microemulsion polymerization method. The microstructure, swellability, filtration, and core flooding performances were tested and characterized. FT-IR spectroscopy indicates that APMS was successfully prepared. Morphological analysis reveals that it is relatively uniform and spherical with an average diameter about 50 nm. Its average diameter increases up to 634 nm after aging at 908C for 7 days in synthetic brine. After aging for 30 days, the particle size is decreased to 482 nm. But the swelling magnification is still 9.6 times its initial diameter. Compared with the traditional microspheres, APMS exhibits excellent thermal stability, salt resistance, and swelling properties. In addition, the plugging factor is in the range of 0.236 to 0.317, and the number of particles for bridge-plugging is slightly increased from 2 to 4 over aging time. Moreover, the plugging parameters show that APMS can favorably enter and effectively plug the artificial cores with permeability of 0.19 to 0.50 mm 2 by deformation, breakthrough and migration, bridging and plugging mechanisms. Furthermore, APMS also shows well its resistance to water flushing and good plugging strength in continuous injection experiment.