Azole antifungals have frequently been linked to the presence of hepatotoxicity, but there is scarce information on cross-toxicity between these drugs or on the possibility of using some of them when this type of toxicity occurs. We report the case of a 64-year-old man with invasive aspergillosis (IA) leading to spondylodiscitis with neurological involvement. Early management included intravenous (iv) voriconazole, which had to be interrupted after 1 week due to liver damage. Therapeutic drug monitoring (TDM) of voriconazole showed that the plasma concentration was within the therapeutic range. However, it was replaced by a combination therapy of oral posaconazole plus iv caspofungin. Posaconazole allowed normalization of liver enzymes. After finishing posaconazole monotherapy on an outpatient basis, the patient made a full recovery. This case report provides further evidence that oral posaconazole is safe and effective as rescue therapy after the appearance of voriconazole-induced liver toxicity.