We evaluate nitrogen oxide (NOx = NO + NO2) production from lightning over the Gulf of Mexico region using data from the Ozone Monitoring Instrument (OMI) aboard NASA’s Aura satellite along with detection efficiency-adjusted lightning data from the World Wide Lightning Location Network (WWLLN). A special algorithm was developed to retrieve the lightning NOx (LNOx) signal from OMI. The algorithm in its general form takes the total slant column NO2 from OMI and removes the stratospheric contribution and tropospheric background and includes an air mass factor appropriate for the profile of lightning NOx to convert the slant column LNO2 to a vertical column of LNOx. WWLLN flashes are totaled over a period of 3 h prior to OMI overpass, which is the time an air parcel is expected to remain in a 1° × 1° grid box. The analysis is conducted for grid cells containing flash counts greater than a threshold value of 3000 flashes that yields an expected LNOx signal greater than the background. Pixels with cloud radiance fraction greater than a criterion value (0.9) indicative of highly reflective clouds are used. Results for the summer seasons during 2007–2011 yield mean LNOx production of ~80 ± 45 mol per flash over the region for the two analysis methods after accounting for biases and uncertainties in the estimation method. These results are consistent with literature estimates and more robust than many prior estimates due to the large number of storms considered but are sensitive to several substantial sources of uncertainty.