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One of the major challenges in treating major depressive disorder (MDD) is patients' non-adherence to medication. This study aimed to explore the barriers and facilitators of patients' adherence to antidepressants among outpatients with MDD.Semi-structured and individual in-depth interviews were conducted among patients with MDD who were taking antidepressants, in the psychiatric clinic of a government-run hospital in Malaysia. Participants were purposively sampled from different genders and ethnicities. Interviews were conducted using a validated topic guide, and responses were audio-recorded, transcribed verbatim, checked, and analyzed using the grounded theory approach.A total of 30 patients were interviewed. Forty different themes and sub-themes were identified which were conceptually divided into two distinct categories related to barriers and facilitators to adherence. The barriers were: patient-specific, medication-specific, healthcare provision and system, social-cultural, and logistics. The facilitators were: having insight, perceived health benefits, regular activities, patient-provider relationship, reminders, and social support networks.Patient-specific barriers and medication side effects were the major challenges for adhering to treatment. Perceived health benefits and having insight on the need for treatment were the most frequently cited facilitators. Targeted interventions should be developed to address the key barriers, and promote measures to facilitate adherence in this group of patients.