The comparative study of patients' profiles and outcomes from pulmonary tuberculosis (TB), before and after the discovery of antibiotic therapy, using sanatoria archives is an unexplored approach in paleopathology. Although higher mortality rates are assumed before chemotherapy, scarce information exists regarding the disease's duration in institutionalized patients and to what extent tuberculous sufferers lived enough to develop skeletal lesions. To fill this gap, 315 clinical files from the former male Sanatorium Carlos Vasconcelos Porto, located in São Brás de Alportel, Portugal, were studied. Two periods of hospitalization were considered: 1931–1944 (n = 128, Group 1) and 1955–1961 (n = 187, Group 2). The average duration of hospitalization (350.3 days for Group 1 and 371.8 for Group 2) and the crude mortality (18.2% and 11.2%, respectively in Groups 1 and 2) did not differ significantly between groups. However, Cox's regression revealed significant differences between survival curves, after adjusting for age at admission (14–74 years old), with pre-chemotherapy patients presenting a higher risk of dying during hospitalization (p = 0.037, hazard ratio = 1.94, IC95% = 1.03–3.63). This study also confirms poorer prognoses for pulmonary tuberculosis sufferers hospitalized in sanatoria before antibiotics and reveals that a significant number of patients survived enough time to develop bone lesions.