Background and Objective Clinical Practice Guidelines (CPGs) provide evidence-based recommendations to healthcare professionals, policy makers, patients and other stakeholders. Mexico is the biggest producer of CPGs in Latin America and Caribbean countries. The National Healthcare Technology Excellence Center (acronym in Spanish: CENETEC) is responsible for the CPG development, adaptation and update. The aim of this study was to assess the Mexican CPG quality and adherence to the GRADE framework. Study design We conducted a descriptive cross-sectional study of 86 CPGs representing all the CPGs produced by CENETEC between 2015 and 2017 and published in an online database called “Catalogo Maestro”. We performed quality assessment with the online AGREE II tool and assessed the reporting on the GRADE framework. Results Of the 86 CPGs, 34 were published in 2015, 21 in 2016 and 31 in 2017. The overall quality by AGREE II proved a median of 16.6% (Min 16.6%, Max 50%). Of the 86 CPGs, 25 (29%) used the GRADE framework; adherence to GRADE standards was, however, inconsistent and generally poor. Conclusion CPGs produced by CENETEC during this period had a low score by AGREE II standards and low adherence to the GRADE framework. A concerted initiative could rapidly improve CENETEC guidelines.