Over half a century ago, McKeown and colleagues proposed that economics was a major contributor to the decline of infectious diseases, including respiratory tuberculosis, during the 19^th and 20^th centuries. Since then, there is no consensus among researchers as to the factors responsible for the mortality decline. Using the case study of the islands of Malta and Gozo, we examine the relationship of economics, in particular, the cost of living (Fisher index) and its relationship to the secular trends of tuberculosis mortality. Notwithstanding the criticism that has been directed at McKeown, we present results that improvement in economics is the most parsimonious explanation for the decline of tuberculosis mortality. We reaffirmed that the reproductively aged individuals were most at risk of dying of tuberculosis, seeing that 70 to 90% of all deaths due to tuberculosis occurred between the ages of 15 and 45. There was a clear sex differential in deaths in that, prior to 1930, rates in females were generally higher than males. During times of extreme hardship, the sex differential was exacerbated. Over the course of World War I, the sex gap in tuberculosis rates increased until peaking in 1918 when there was also the influenza pandemic. The heightened differential was most likely a result of gendered roles as opposed to biological differences since female tuberculosis rates again surpassed male rates in 1945 during World War II. Respiratory tuberculosis in both urban and rural settlements (in Malta proper) was significantly influenced by the Fisher index, which explains approximately 61% of the variation in TB death rates (R = 0.78; p<0.0001). In Gozo, there was no significant impact on respiratory tuberculosis (R = 0.23; p = 0.25), most likely a consequence of the island’s isolation, a self-sufficient economy and limited exposure to tuberculosis.