Background: The Covid-19 pandemic is characterized by extreme variability in the outcome distribution and mortality rates across different countries. Some recent studies suggested an inverse correlation with BCG vaccination at population level, while others denied this hypothesis. In order to address this controversial issue, we performed a strict epidemiological study collecting data available on a global scale, considering additional variables such as cultural-political factors and adherence to other vaccination coverages. Methods: Data on 121 countries, accounting for about 99% of Covid-19 cases and deaths globally, were from John’s Hopkins Coronavirus Resource Center, World Bank, International Monetary Fund, United Nations, Human Freedom Report, BCG Atlas. Statistical models were Ordinary Least Squares, Tobit and Fractional Probit, implemented on Stata/MP16 software. Results: Countries where BCG vaccination is or has been mandated in the last decades have seen a drastic reduction in Covid-19 diffusion (-80% on average) and mortality (-50% on average), even controlling for relative wealth of countries and their governmental health expenditure. A significant contribution to this reduction (respectively -50% and -13% on average) was also associated to the outbreak onset during summer, suggesting a possible influence of seasonality. Other variables turned out to be associated, though to a lesser extent. Conclusions: Relying on a very large dataset and a wide array of control variables, our study confirms a strong and robust association between Covid-19 diffusion and mortality with BCG vaccination and a set socio-economic factors, opening new perspectives for clinical speculations, experimental studies and public health policies.