Nitrous oxide (N2O) is an important ozone-depleting gas and greenhouse gas with multiple uncertain emission processes. Global nitrous oxide observations, the Model of Atmospheric Transport and Chemistry (MATCH) and an inverse method were used to optimally estimate N2O emissions from twelve source regions around the globe. MATCH was used with forecast center reanalysis winds at T62 resolution (192 longitude by 94 latitude surface grid, and 28 vertical levels) from 1 July 1996 to 30 June 2006. The average concentrations of N2O in the lowest four layers of the model were then compared with the monthly mean observations from four national/international networks measuring at 65 surface sites. A 12-month-running-mean smoother was applied to both the model results and the observations, due to the fact that the model was not able to reproduce the very small observed seasonal cycles. The inverse method was then used to solve for the time-averaged regional emissions of N2O for two time periods (1 January 1997 to 31 December 2001 and 1 January 2002 to 31 December 2005). The best estimate inversions assume that the model stratospheric destruction rates, which lead to a global N2O lifetime of 125 years, are correct. It also assumes normalized emission spatial distributions within each region from Bouwman et al. (1995). We conclude that global N2O emissions with 66% probability errors are 16.3−1.2+1.5 and 15.4−1.3+1.7 TgN (N2O) a−1, for 1997–2001 and 2001–2005 respectively. Emissions from the equator to 30°N increased significantly from the initial Bouwman et al. (1995) estimates while emissions from southern oceans (30°S–90°S) decreased significantly. The quoted uncertainties include both the measurement errors and modeling uncertainties estimated using a separate flexible 12-box model. We also found that 23 ± 4% of the N2O global total emissions come from the ocean, which is slightly smaller than the Bouwman et al. (1995) estimate. For the estimation of emissions from the twelve model regions, we conclude that, relative to Bouwman et al. (1995), land emissions from South America, Africa, and China/Japan/South East Asia are larger, while land emissions from Australia/New Zealand are smaller. Our study also shows a shift of the oceanic sources from the extratropical to the tropical oceans relative to Bouwman et al. (1995). Between the periods 1997–2001 and 2002–2005, emissions increased in China/Japan/South East Asia, 0°–30°N oceans, and North West Asia and decreased in Australia/New Zealand, 30°S–90°S oceans, 30°N–90°N oceans, and Africa. The lower tropical ocean emissions in 1997–2001 relative to 2002–2005 could result from the effects of the 1997–1998 El Nino in the earlier period.