The influence of masonry infills with eccentric openings on the seismic performance of reinforced concrete (r/c) frames that were designed in accordance with current code provisions are investigated. Eight 1/3-scale, single-story, single-bay frame specimens were tested under cyclic horizontal loading up to a drift level of 4%. In all examined cases the shear strength of columns was higher than the cracking shear strength of solid infill. The parameters investigated include the shape and the location of the opening. Assessment of the behavior of the frames is also attempted, based on the observed failure modes, strength, stiffness, ductility, energy dissipation capacity and degradation from cycling loading. Based on these results there can be deduced that masonry infills with eccentrically located openings has been proven to be beneficial to the seismic capacity of the bare r/c frames in terms of strength, stiffness, ductility and energy dissipation. The location of the opening must be as near to the edge of the infill as possible in order to provide an improvement in the performance of the infilled frame.