Aspergillus spp. often colonize the respiratory tract of the critically ill patients in the intensive care units and subsequently cause invasive disease. The risk of developing invasive disease is more in immunocompromised patients. Here we report a case of fatal invasive pulmonary aspergillosis caused by Aspergillus versicolor in a post-operative patient on mechanical ventilation, who did not respond to intravenous itraconazole. We have discussed the challenges involved in accurate diagnosis of this condition and appropriate management.