AbstractPoly(cyclic imino ether)s (PCIE) have emerged as a highly promising class of polymer for use in biomedical applications with their value being derived from their excellent biocompatibility, diverse chemistry, and tunable hydrophilicity. Here, we investigate the properties of poly(2‐isopropyl‐2‐oxazine) (PiPrOz), a relatively unexplored PCIE, determining it to have a cloud point temperature (T_cp) below physiological temperature, not to crystallize from bulk or in solution, and to be highly biocompatible. Furthermore, a series of copolymers consisting of iPrOz and 2‐methyl‐2‐oxazine (MeOz) was investigated with regard to the effect of monomer distribution and polymer architecture on thermoresponsive properties. To this end, linear block and statistical co‐poly(2‐oxazine)s (co‐POz), along with three comb‐shaped POz with block or statistical POz side chains were prepared. Each of the five polymers showed distinct thermoresponsive behavior, with the linear block co‐POz undergoing micelle formation and the other polymers macroscopic phase‐separation at different T_cps. The variety observed in response to heating clearly highlights the importance of monomer sequence and polymer architecture when designing thermoresponsive polymers. We anticipate that our findings will prove useful to polymer chemists seeking to prepare novel thermoresponsive biomaterials.