Arbuscular mycorrhizal fungi arguably form the most successful and wide-spread endosymbiosis with plants. In general terms there is very little host-specificity in this interaction, indicating an extremely broad compatibility. However, host preferences as well as varying symbiotic efficiencies have been observed, the molecular basis of which is still largely unknown. Secreted proteins (SPs) may act as fungal effectors to control symbiotic efficiency in a host-dependent manner. Therefore, we studied whether AM fungi adjust their secretome in a host- and stage-dependent manner to contribute to their extremely wide host-range. We investigated the expression of SP encoding genes of R. irregularis DAOM197198 in three evolutionary distantly related plant species, Medicago truncatula (Medicago), Nicotiana benthamiana (Nicotiana) and Allium schoenoprasum (Chives). In addition we used laser microdissection in combination with RNAseq to study SP expression at different stages of the symbiotic interaction in Medicago. Our data indicate that the vast majority of 288 expressed SPs show equal expression levels in the interaction with all three host plants. In addition, a subset (~15%) of the SPs show significant differential expression depending on the host plant and/or environmental condition. This host-dependent expression appears to be controlled locally in the hyphal network in response to host metabolic cues. Overall, this study offers a comprehensive analysis of the R. irregularis secretome, which now offers a solid basis to direct functional studies on the role of fungal SPs in AM symbiosis.