Background: Examining the anti-hypertensive regimens of individuals with different comorbidities may offer insights into how we can improve hypertension management. Methods: The Medical Expenditure Panel Survey (2013–2015) was used to describe the most common single-, two-, three-, and four-drug hypertension regimens among hypertensive adults in four different comorbidity groups: 1. Hypertension only; 2. Hypertension and diabetes; 3. Hypertension and cardiovascular disease (coronary heart disease or stroke history); and 4. Hypertension, diabetes, and cardiovascular disease. Results: 15,901 adults with hypertension taking anti-hypertensive medications were included in the study. 58.6% (95% CI: 57.3–59.8) took multiple anti-hypertensive medications, but the proportion of adults taking multiple anti-hypertensives varied by comorbidity group. Regimens including an ACE-inhibitor/ARB were the most prevalent regimens among individuals taking >2 anti-hypertensive medications. The most common two-drug regimen for both the hypertension-only and hypertension-diabetes groups was an ACE-inhibitor/ARB with thiazide. The most prevalent regimen for the two cardiovascular disease groups was an ACE-inhibitor/ARB with beta-blocker. Conclusions: Most individuals with hypertension use between 2–5 medications and the medications comprising these regimens vary by comorbidity. The ACCOMPLISH trial suggested that certain combinations may lead to superior cardiovascular outcomes. Research comparing the efficacy of different hypertension medication combinations among individuals with different comorbidities could lead to better patient hypertensionrelated outcomes.