Abstract Objectives Breast sensation following autologous breast reconstruction impacts patients’ quality of life. Although spontaneous reinnervation in free flaps was documented by many authors, there are efforts to further improve restoration of breast sensation. Interestingly, animal studies indicated that trastuzumab has several beneficial effects on transected peripheral nerves. Our aim was to compare spontaneous sensory recovery after free TRAM flap breast reconstruction between patients who were and were not treated with trastuzumab. Methods The study included 14 subjects who underwent tactile sensation examination in 5-year period after noninnervated free muscle-sparing TRAM flap breast reconstruction at the University Hospital Centre Zagreb, Croatia. Small and large flap skin islands and contralateral healthy breasts were tested with Semmes-Weinstein type monofilaments. Three sensory scores were created to more accurately compare breast sensation. Results In subjects receiving trastuzumab, sensory recovery earlier extended to at least four of five large skin island regions and was always present in the central flap area in comparison with subjects who were not administered trastuzumab (p=0.0476). As indicated by total sensory scores, trastuzumab-treated subjects restored sensation better resembling healthy control breasts (54 vs. 39 % in large skin islands; 95 vs. 71 % in small skin islands). Conclusions To the authors’ knowledge, the current study for the first time demonstrated trastuzumab’s potential to improve sensory outcomes in human. Our results support the strategy that accelerated nerve regeneration is a key to more successful reinnervation. HER2 and EGFR inhibitors emerge as new candidates for pharmacological interventions in peripheral nerve injury treatment.