The prevalence of penicillin-resistant Streptococcus pneumoniae (PRSP) meningitis has increased worldwide, particularly in East Asia and the United States. We recently experienced a case of PRSP meningitis that developed during frontofacial distraction. The patient was a 7-year-old girl with Crouzon disease who was treated by frontofacial monobloc/Le Fort IV minus glabellar osteotomy with quadruple internal distraction devices. Penicillin-resistant Streptococcus pneumoniae meningitis was diagnosed after surgery and treated successfully with meropenem (a carbapenem) at 120 mg kg d every 8 hours, ceftriaxone (a third-generation cephalosporin) at 100 mg kg d every 12 hours, and vancomycin (a glycopeptide) at 45 mg kg d every 6 hours. This case indicates that severe and fatal bacterial meningitis may occur as a postoperative complication due to multidrug-resistant bacteria indigenous to the nasal cavity after simultaneous osteotomy of the cranium and facial bone in intracraniofacial surgery, such as that for syndromic craniosynostosis and hypertelorbitism. In such cases, preventive strategies should include preoperative administration of pneumococcal vaccine, preoperative screening of nasal bacterial flora by nasal culture test, and prior administration of a carbapenem with good cerebrospinal fluid transfer or a third- or fourth-generation cephem covering PRSP. Postoperatively, suspected meningitis may be treated with a combination of the 3 drugs used in our case, in parallel with emergency cephalic contrast computed tomography and culture tests of blood and cerebrospinal fluid. Our experience suggests that these measures will facilitate a successful outcome in frontofacial distraction osteogenesis.