Here, we report a pH-controlled stereoregular polymerization of methyl methacrylate (MMA) inside the membrane of H20-COOH hyperbranched polymer vesicles using a common radical polymerization process. The vesicle size decreases from 745 to 214 nm with an increase of solution pH from 2.60 to 7.26, and the isotacticity of the obtained polymethyl methacrylates (PMMAs) is accordingly elevated from 9 to 35%. The obtained isotactic-rich PMMAs show a lower glass transition temperature depending on the isotacticity than the commercial random PMMAs. A mechanism study according to the in situ Fourier transform infrared measurements indicates that the control of polymer isotacticity results from the monomer conformation confined effect inside the thin vesicle membranes. The present study provides a new method to realize the preparation of isotactic polymers with the characteristics of facile synthesis, pH controllability, and a green polymerization process in aqueous solution as well as under mild reaction conditions of ambient temperature and pressure.