This paper summarizes the different activities undertaken in order to identify the main causes of the collapse of the Space Building, a 27-story reinforced concrete framed building in Medellín, Colombia. Site investigations, field and laboratory tests, and a detailed analytical work including structural analysis under different considerations were carried out. The main cause of the collapse was associated with the deficient structural capacities of the columns of the building in relation to the dead and service loads imposed at the time of the collapse. The occurrence of high differential settlements, the high compressive stresses in main columns, the repair works that were carried out minutes before the collapse, and the probable shear failure of beams and compressive failure of partitions walls during repair works were identified as probable secondary causes and detonating factors of the building collapse. The authors of this investigation considered that if the building had been designed adequately using the Colombian building design codes available at that time, it would not have collapsed, even if most of the aforementioned detonating events had occurred.