BACKGROUND: Carbon dioxide (CO(2)) laser provides precision and excellent hemostasis, leading to healing with minimal discomfort and complications. In spite of the advantages, the application of CO(2) laser has been limited in the sinonasal region due to the difficulty in delivering laser energy to the deep, narrow, and confined spaces. The availability of flexible laser fibers and custom-designed hand pieces has rectified these limitations but, until this date, there are no data on their safety and efficacy profile. METHODS: We conducted a retrospective chart review of patients who underwent sinonasal and nasopharyngeal surgery with a hand-held CO(2) laser at M.D. Anderson Cancer center between 2007 and 2009. RESULTS: Out of 12 patients, 3 patients had postradiotherapy adhesions, 2 patients had a recurrent sinonasal mucoepidermoid carcinoma and 1 patient each had a ganglioneuroblastoma of the nasopharynx involving the basisphenoid and clivus, recurrent spindle cell melanoma of the nasopharynx, juvenile nasopharyngeal angiofibroma, papilloma of the nasal cavity, pituitary adenoma, spindle cell lipoma of the nasopharynx, and intranasal Rosai-Dorfman disease. The CO(2) laser, along with conventional endoscopic techniques and instruments, was used at 6-12 W continuous mode, to excise the disease. Median blood loss was 88 mL with no laser-related complication in any patient. CONCLUSION: In sinonasal and nasopharyngeal regions, use of hand-held CO(2) laser fiber provides precision, excellent hemostasis and minimizes tissue manipulation thereby reducing risk to the underlying structures. Thus, it can be an important tool for rhinologists and skull-base surgeons, especially for revision and postradiotherapy cases.