Background: Health-system barriers and facilitators associated with cardiovascular medication adherence have seldom been studied, particularly in low- and middle-income countries where uptake rates are poorest., Objectives: This study sought to explore the major obstacles and facilitators to the use of evidence-supported medications for secondary prevention of cardiovascular disease using qualitative analysis in 2 diverse countries across multiple levels of their health care systems., Methods: A qualitative descriptive study approach was implemented in Hamilton, Ontario, Canada, and Delhi, India. A purposeful sample (n = 69) of 23 patients, 10 physicians, 2 nurse practitioners, 5 Department of Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homoeopathy physicians, 11 pharmacists, 3 nurses, 4 hospital administrators, 1 social worker, 3 nongovernmental organization workers, 2 pharmaceutical company representatives, and 5 policy makers participated in interviews in Hamilton, Ontario, Canada (n = 21), and Delhi, India (n = 48). All interviews were digitally recorded and transcribed followed by directed content analysis to summarize and categorize the interviews., Results: Themes that emerged across the stakeholder groups included: medication counseling; monitoring adherence; medication availability; medication affordability and drug coverage; time restrictions; and task shifting. The depth of verbal medication counseling provided varied substantially between countries, with prescribers in India unable to convey relevant information about drug treatments due to time constraint and high patient load. Canadian patients reported drug affordability as a common issue and very few patients were familiar with government subsidized drug programs. In India, patients purchased medications out-of-pocket from private, community pharmacies to avoid long commutes, lost wages, and unavailability of medications from hospitals formularies. Task shifting medication-refilling and titration to nonphysician health workers was accepted and supported by physicians in Canada but not in India, where many of the physicians considered a high level of clinical expertise a precondition to carry out these tasks skillfully., Conclusions: Our findings reveal context-specific, health system factors that affect the patient's choice or ability to initiate and/or continue cardiovascular medication. Strategies to optimize cardiovascular drug use should be targeted and relevant to the health care system., (Copyright © 2017 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.)