We report a case of a 41-year-old woman, wearer of contact lenses who was presented to the emergency room with a 2-month history of pain and red eye. She presented with a severe keratitis refractory to quinolones, fortified antibiotics and clotrimazole. Due to the risk of perforation, a tectonic penetrating keratoplasty (PK) was performed. Clinical signs of keratitis recurrence were observed and cultures were positive for Purpureocillium lilacinum ( former Paecilomyces lilacinus) . The patient did not improve on topical amphotericin B and intracameral voriconazole. Worsening of clinical condition required a new PK. Oral posaconazole was initiated postoperatively and suspended at the fourth postoperative month. The cornea remains clear until the last follow-up visit, 12 months after the second graft. To our knowledge, this is the second case report that documents the effectiveness of oral posaconazole in a refractory P. lilacinus keratitis, resistant to other second-generation triazoles and conventional antifungals.