Post-sternotomy infectious complications, including superficial and deep wound infections, sternal osteomyelitis and mediastinitis, are rarely caused by fungi. Trichosporon asahii is the main Trichosporon species that causes systemic infection in humans. Most cases involved neutropenic patients with hematologic malignancies. We report a unique case of a non-cancer, non-neutropenic but severely ill patient who developed an ultimately lethal T. asahii infection after sternotomy. We speculate that our patient had been colonized with the fungus and his surgical site infection may have been related to his emergency revascularization surgery. Therapy with liposomal amphotericin failed to sterilize the bloodstream despite in vitro susceptibility results. The addition of voriconazole helped sterilizing the bloodstream without changing the outcome. Physicians must be aware of the continuously expanding spectrum of infections with this emerging difficult-to-treat fungal pathogen.