Self-healing materials and, in particular, polymers are characterized by their ability to partially or fully restore their original properties or functions after damage. Amongst the healable polymer classes, thermoplastic polyurethanes have received increasing attention in the last years. This is mainly due to their broad application areas, the variety of chemical platforms that can be used, and the potential use of hydrogen bonding to assist the healing process. However, the combination of good mechanical properties and healing at near room temperature remains challenging. In order to learn how to find a better balance between healing and mechanical properties, dedicated studies on the impact of the monomer chemical architecture on the overall polymer performance are needed.In this work we study the impact of monomer mixtures with different chemical composition on the overall mechanical and healing behaviour of self-healing thermoplastic polyurethanes based on CroHeal™ 2000, biopolyol. The polymers are synthesized via one-shot technique, starting from three constituents: a long chain diol (CroHeal™ 2000), a chain extender (EHD) and a diisocyanate (aromatics - MDI and PPDI, and aliphatic - HMDI) or diisocyanate mixtures (MDI/HMDI and MDI/PPDI in different ratios).Fracture tests using Single Edge Notch Tension specimens show a clear increase in mechanical properties and interfacial strength recovery after damage for short healing times at room temperature when using higher aromatic content in the isocyanate mixture. Furthermore, IR mapping showed that initial compositional heterogeneity is decreased when more aliphatic isocyanates are used but also when longer annealing times are applied in the case of aromatic diisocyanates. The presence of compositional heterogeneities does not influence the healing response under the conditions studied.