Friction stir welding (FSW) is a solid state welding process used to weld difficult to be welded or unweldable materials as aluminium alloys. In the last years, other materials have been successfully tested as magnesium, titanium and nickel based alloys. Dissimilar joints can be obtained by FSW, but issues arise concerning the correct choice of the process parameters. In the paper, the results of an experimental and numerical campaign aimed to produce dissimilar AZ31-AA6016-T6 butt joints are presented. The effect of sheet mutual position and main process parameters was investigated. It was found that intermetallics are the main cause of the poor quality of the joints. Sound joints can be produced only if the magnesium alloy is in the advancing side.