Exterior walls in historic multi-storey buildings compared to walls in modern buildings have low thermal resistance, resulting in high energy loss and cold surfaces/floors in cold climates. When restrictions regarding alteration of the exterior appearance exist, interior insulation might be the only possibility to increase occupant comfort. This paper describes an investigation of the hygrothermal influence when applying 100 mm of diffusion open interior insulation to a historic multi-storey solid masonry spandrel. The dormitory room with the insulated spandrel had a normal indoor climate with a maximum observed monthly average humidity by volume excess of 3.2 g/m3 during the experiment. Relative humidity and temperature were monitored manually using wooden dowels over 2 years and 8 months in two solid masonry spandrels: one insulated wall and one untreated wall. The investigation showed that installing insulation on a solid masonry spandrel induced hygrothermal changes: Uniformly distributed higher relative humidity and lower temperature throughout the masonry, compared to an un-insulated wall. The relative humidity of the un-insulated masonry wall was in the range 50% on the inside to 60% on the outside, while the insulated wall showed uniformly distributed values around 80%. The risk of moisture-induced damage was evaluated based on mathematical models for mould and decay of wood, visual inspection for frost and mould, and on-site measurements for presence of mould spores. The damage evaluation showed no risk of damage from the changed hygrothermal conditions when applying interior insulation to a solid masonry spandrel.