Models using medication-based predictors can predict a substantial part of five-year all-cause mortality in COPD patients and may serve as a useful proxy for clinical, physiological, laboratory, and imaging predictors, which are often unavailable in medico-administrative databases and/or inaccessible to physicians in routine practice; they may also yield additional gains in predictive discrimination when combined with these other sources. While ML approaches, especially D-ANN, showed improved performance, gains over logistic regression were modest.