Use of multiple prescription medications is common among individuals with chronic obstructive pulmonary disease (COPD) because of coexisting inflammatory-related conditions. Specifically, the use of antidepressants, inhaled corticosteroids (ICSs), and statins may place individuals with COPD at high risk for new-onset diabetes. The objective was to examine the relationship between the use of antidepressants, ICSs, and statins and new-onset diabetes among Medicaid beneficiaries with COPD. This study used a retrospective longitudinal cohort design using multiple years (2005-2008) of Medicaid claims for beneficiaries with newly diagnosed COPD (n = 15,287), who were diabetes free at baseline. National Drug Codes were used to determine the receipt of antidepressants, ICSs, and statins, and International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to define new-onset diabetes (250.x2). Multivariable logistic regression was used to examine the adjusted relationship between medication use and new-onset diabetes. Overall, 6.3% of the study population was diagnosed with new-onset diabetes. After controlling for baseline characteristics, individuals using ICSs (adjusted odds ratio [AOR]: 1.23; 95% confidence interval [CI]: 1.07, 1.47) or statins (AOR: 1.48; 95% CI: 1.27, 1.72) had a greater risk of new-onset diabetes compared to those not given ICSs, statins, or antidepressants. Analyses using combined medication categories revealed that adults using statins in combination with both antidepressants and ICSs, or when combined with ICS, were more likely to have new-onset diabetes. These findings indicate that multiple medication use (ICSs and statins) was associated with increased rates of new-onset diabetes. Further research is warranted to understand this association.