This paper shows the potential of a multicalibration approach for reducing fuel consumption while keeping pollutant immissions. The paper demonstrates that the current engine control approach with a single fixed calibration involves important fuel penalties in areas with low vehicle densities where local pollution is not an issue, while the NOx emissions in urban areas are usually too high to fulfill air quality standards. The proposed strategy is based on using information about the vehicle location and the NOx concentrations in the ambient to choose a suitable calibration amongst a set of possibilities. To assess the potential of such a strategy experimental tests have been done with a state-of-art turbocharged Diesel engine. First, a design of experiments is used to obtain three different calibrations. The first one is aimed to minimize NOx emissions with some constraints in the actuations, the second one, is focused on minimizing fuel consumption with constraints in the maximum NOx emissions allowed, while the third one minimized fuel consumption without NOx restrictions. Then a set of driving conditions, containing both standard cycles and real driving cycles are tested in an engine-in-the-loop approach to evaluate the engine performance and emissions with the developed calibrations. Finally, the combination of the obtained calibrations shows that fuel consumption in non-urban areas can be reduced about a 6% without damaging the air quality, while fuel penalties around 2% are necessary to keep air quality standards in metropolitan areas.