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Masonry infill walls are the most traditional enclosure system that is still widely used in RC frame buildings all over the world, particularly in seismic active regions. Although infill walls are usually neglected in seismic design, during an earthquake event they are subjected to in-plane and out-of-plane forces that can act separately or simultaneously. Since observations of damage to buildings after recent earthquakes showed detrimental effects of in-plane and out-of-plane load interaction on infill walls, the number of studies that focus on influence of in-plane damage on out-of-plane response has significantly increased. However, most of the xperimental campaigns have considered only solid infills and there is a lack of combined in-plane and out-of-plane experimental tests on masonry infills with openings, although windows and doors strongly affect seismic performance. In this paper, two types of experimental tests on infills with window openings are presented. The first is a pure out-of-plane test and the second one is a sequential in-plane and out-of-plane test aimed at investigating the effects of existing in-plane damage on outof-plane response. Additionally, findings from two tests with similar load procedure that were carried out on fully infilled RC frames in the scope of the same project are used for comparison. Test results clearly show that window opening increased vulnerability of infills to combined seismic actions and that prevention of damage in infills with openings is of the utmost importance for seismic safety.