BACKGROUND: Cigarette smoke contributes to skeletal muscle wasting. While exercise and nutritional therapies are effective in improving skeletal muscle quantity and quality, the effect of medications on longitudinal muscle loss is unclear. We investigated whether long-term use of common medications affects longitudinal skeletal muscle changes in current and former smokers. METHODS: Using quantitative computed tomography imaging, we measured the 5-year changes in pectoralis muscle area (delta-PMA) and pectoralis muscle density (delta-PMD) of 4191 participants in the COPD Genetic Epidemiology (COPDGene RESULTS: Over the study period, the median delta-PMA for the entire population showed a decrease of 2.23cm CONCLUSION: In current and former smokers, statin use was associated with reduced pectoralis muscle wasting, while aspirin use was associated with increased muscle loss. Additional research is needed to verify these findings. (Clinicaltrials.gov identifier NCT00608764).