Abstract: Urea has become the predominant source of synthetic nitrogen (N) fertilizer used throughout the world. Among the various available mitigation tools, urease inhibitors like NBPT have the most potential to improve efficiency of urea by reducing N losses, mainly via ammonia volatilization. However, there is a lack of information on the effect of N-(n-butyl) thiophosphoric triamide (NBPT) on other N losses such as gaseous emissions of N2O and NO and NO3− leaching. A two-year field experiment using irrigated maize (Zea mays) crop was carried out under Mediterranean conditions to evaluate the effectiveness of urea coated with NBPT (0.4%, w/w) alone and with both NBPT and nitrification inhibitor dicyandiamide (DCD) (0.4 and 3%, w/w, respectively) to mitigate N2O–N, NO–N and NO3−–N losses. The different treatments of U, U+NBPT and U+NBPT+DCD were applied to the maize crop in 2009 and then in 2010. The 2010 maize crop followed a fallow period, during which the 2009 crop residues were incorporated into the soil. Two different irrigation regimes were followed each year. In 2009, irrigation was controlled for the first 2 weeks following urea fertilization; whereas, the 2010 crop period was characterized by increased irrigation in the same period. After each treatment application, measurements of the changes in soil mineral N, gaseous emissions of N2O and NO, nitrate leaching and biomass production were made. N2O emissions were effectively abated by NBPT and NBPT+DCD and were reduced by 54 and 24%, respectively, in 2009. A reduction in nitrification rate by the inhibitors was also observed during 2009. In 2010 cropping period, NBPT reduced N2O emissions by 4%; while the combination of NBPT and DCD treatment reduced N2O emission by 43%. Yield-scaled N2O emissions were reduced by 50 and 18% by NBPT and the mixture of NBPT+DCD, respectively, in 2009. Applying inhibitors did not have any significant effect on yield-scaled N2O emissions in the 2010 crop period. Total NO losses from urea were 2.25 kg NO–N ha−1 in the 2009 crop period and 5 times lower in the following year; this may provide an indicator of the prevalence of nitrification as the main process in the production of N2O in the 2009 maize crop. Most of the NO3− was lost within the fallow period (i.e. 92, 81 and 75% of the total NO3− leached for U, U+NBPT and U+NBPT+DCD, respectively), so the incorporation of crop residues was not as effective as expected at reducing these N losses. Our study suggests that the effectiveness of NBPT and combination of NBPT+DCD in reducing N losses from applied urea is influenced by management practices, such as irrigation, and climatic conditions.