Factors associated with therapeutic lifestyle change (TLC) after myocardial infarction (MI) have not been fully investigated in Chile. This study aimed to provide a descriptive examination of facilitators and barriers to TLC after first MI. Methods: Qualitative study based on in-depth interviews and focus groups with cardiologists and patients who had first MI one-year±2 months before the begin-ning of the study. Grounded theory research methods were used to guide sampling and coding of data. Results: Twenty-one patients who had first myocardial infarction and 14 cardiologists participated in in-depth interviews and focus groups until the point of theoretical saturation. Facilitators for TLC included optimism, self-efficacy, faith-based life purpose, positive attitudes by family and friends, social participation, good patient-physician relationship, and positive medical advice. Barriers were: individual (older age, female sex, lower educational level, limiting beliefs, ambi val ence, depressive mood, lack of knowledge on strategies to achieve TLC, financial constraints), family (family crisis, overprotection, im-posing attitudes, unhealthy habits at home), work (work overload and competition between work recovery and TLC), socio-environmental (neighborhood unsafety), and health provider-related (poor patient-physician re-lationship, limiting beliefs among physicians, medical advice centered on restrictions or imprecise, medical training focused on pharmacological therapies and in-terventional procedures over preventive care, and orga-nizational issues). Conclusions: Reported facilitators and barriers enhance understanding of the process of lifestyle change after first myocardial infarction, and might be targets for optimization of secondary preventive strategies among Chilean patients.