This volume constitutes the proceedings of the 16th International Conference of the CLEF Association on Experimental IR Meets Multilinguality, Multimodality, and Interaction, CLEF 2025, held in Madrid, Spain, during September 9–12, 2025. The 25 full papers included in this book were carefully reviewed and selected from 33 submissions. They were organized in the following sections: Conference Papers; Best of CLEF 2024 Labs; and Condensed Labs Overviews.