Objective: Despite major advances in research on acute stroke care interventions, relatively few stroke patients benefit from evidence-based care due to multiple barriers. Yet current evidence of such barriers is predominantly from high-income countries. This study seeks to understand stroke care professionals' views on the barriers which hinder the provision of optimal acute stroke care in Ghanaian hospital settings. Design: A qualitative approach using semistructured interviews. Both thematic and grounded theory approaches were used to analyse and interpret the data through a synthesis of preidentified and emergent themes. Setting: A multisite study, conducted in six major referral acute hospital settings (three teaching and three non-teaching regional hospitals) in Ghana. Participants: A total of 40 participants comprising neurologists, emergency physician specialists, non-specialist medical doctors, nurses, physiotherapists, clinical psychologists and a dietitian. Results: Four key barriers and 12 subthemes of barriers were identified. These include barriers at the patient (financial constraints, delays, sociocultural or religious practices, discharge against medical advice, denial of stroke), health system (inadequate medical facilities, lack of stroke care protocol, limited staff numbers, inadequate staff development opportunities), health professionals (poor collaboration, limited knowledge of stroke care interventions) and broader national health policy (lack of political will) levels. Perceived barriers varied across health professional disciplines and hospitals. Conclusion: Barriers from low/middle-income countries differ substantially from those in high-income countries. For evidence-based acute stroke care in low/middle-income countries such as Ghana, health policy-makers and hospital managers need to consider the contrasts and uniqueness in these barriers in designing quality improvement interventions to optimise patient outcomes.