© 2017 Royal Australasian College of Physicians. This article has been contributed to by US Government employees and their work is in the public domain in the USA. Background: In the elderly, impaired cognition may weaken medication adherence and compromise treatment for cardiovascular disease (CVD). Aim: We examined risk factors for medication adherence and the relationship between adherence and levels of CVD risk factors among older participants with hypertension, dyslipidaemia and diabetes in the Framingham Heart Study. Methods: The four-item Morisky Medication Adherence Scale was administered to 1559 participants, median age 70 years, 53% women. We created an adherence score, ranging from 0 to 4, with low adherence defined as a score ≥2. CVD risk factors were assessed using standard protocols. Cognition was measured using the Mini-Mental State Examination (MMSE) and depressive symptoms were measured using the Center for Epidemiologic Studies of Depression (CES-D) scale. Results: Among participants who self-reported taking antihypertensive, lipid-lowering and/or hyperglycaemic medication(s), 12% (n = 191) had low medication adherence. The risk of low adherence increased by 45% (95% confidence interval (CI): 25–68%, P < 0.001) per five-unit increase in CES-D score. In participants taking antihypertensive medication (n = 1017), low adherence was associated with higher mean diastolic blood pressure (73 mmHg, 95% CI: 71–75 vs 71 mmHg, 95% CI: 70–71; P = 0.04) after adjusting for covariates. Among participants taking lipid-lowering medication (n = 937), low adherence was associated with higher mean low-density lipoprotein cholesterol (92 mg/dL, 95% CI: 87–96 vs 86 mg/dL, 95% CI: 84–88; P = 0.03). Low adherence was not associated with fasting plasma glucose (P = 0.10) or haemoglobin A1c (P = 0.68) in the subgroup of participants (n = 192) taking hypoglycaemic medication. Conclusions: Depressive symptoms might act as a barrier for medication adherence, which exacerbates CVD risk factors in older-aged adults.