Evapotranspiration (ET) is the second largest component of the water cycle in arid and semiarid environments, and, in fact, more than 60% of the precipitation on earth is returned to the atmosphere through it. MOD16 represents an operational source of ET estimates with adequate spatial resolution for several applications, such as water resources planning, at a regional scale. However, the use of these estimates in routine applications will require MOD16 evaluation and validation using accurate ground-based measurements. The main objective of this study was to evaluate the performance of the MOD16A2 product by comparing it with eddy covariance (EC) systems. Additional objectives were the analysis of the limitations, uncertainties, and possible improvements of the MOD16-estimated ET. The EC measurements were acquired for five sites and for a variety of land covers in northwestern Mexico. The indicators used for the comparison were: root mean square error (RMSE), bias (BIAS), concordance index (d), and determination coefficient (R 2) of the correlation, comparing measured and modelled ET. The best performance was observed in Rayón (RMSE = 0.77 mm•day −1 , BIAS = −0.46 mm•day −1 , d = 0.88, and R 2 = 0.86); El Mogor and La Paz showed errors and coefficients of determination comparable to each other (RMSE = 0.39 mm•day −1 , BIAS = −0.04 mm•day −1 , R 2 = 0.46 and RMSE = 0.42 mm•day −1 , BIAS = −0.18 mm•day −1 , R 2 = 0.45, respectively). In most cases, MOD16 underestimated the ET values.