Purpose: To determine the efficacy of near-infrared spectroscopy (NIRS) in identifying the hemisphere associated with language by measuring changes in bilateral lateral inferior frontal blood flow during a word generation task in epilepsy surgery patients and healthy volunteers. Methods: Sixteen patients who underwent the intracarotid amobarbital procedure (IAP) and eight healthy right-handed/right-footed individuals were tested with NIRS during a word generation paradigm. Results: Increases in lateral inferior frontal total hemoglobin concentrations agreed with the IAP in 11 of 16 patients, including 2 of 3 with right hemisphere (atypical) speech dominance (P=0.13). NIRS revealed increases in lateral inferior frontal total hemoglobin concentrations congruent with language dominance predicted by handedness/footedness in 18 of 24 subjects, including 100% of healthy right-handed subjects (P=0.02). Conclusion: NIRS is a simple, non-invasive, safe modality for measuring cerebral blood flow. Further research and development of testing procedures and instrumentation are needed before routine implementation in pre-surgical testing.