Background and objectives: Inadequate adherence has been recognized as a constant determinant in the overall burden of ischemic heart disease, particularly in countries with higher income-health inequalities, such as Mexico. The overall impression is that the lack of population-based epidemiological data and low public awareness may account for this problem. This study aimed to determine the level of adherence to secondary cardiovascular prevention therapy in a tertiary hospital in Mexico City and identify the barriers contributing to medication nonadherence. Methods: A cross-sectional study was conducted in the cardiology outpatient department between August 2018 and February 2020. Participants were asked about socio-demographic data, the MMAS-4, and an interview regarding reasons for nonadherence. Results: A total of 991 patients were included, with a median age of 65 (58,72) years old. Inadequate adherence to treatment was reported by 70.3%, with forgetfulness as the most frequent cause (55.4%). Patients on combined pharmacological therapy with PCI or CABG were more adherent than those on optimal medical therapy alone. A higher proportion of patients in the inadequate group were in NYHA classes II and III. Low educational level and the use of optimal medical treatment alone were predictors for poor adherence. Conclusion: These findings provide an initial framework of the current situation of adherence to secondary prevention therapy in Mexico, highlighting the value of promoting national consensus on medication adherence to move towards a population-based strategy to reduce cardiovascular disease burden.