IntroductionPremature myocardial infarction (MI) generally refers to MI in men ≤55 years or women ≤65 years. Premature MI is a major contributor to cardiovascular disease (CVD), which claimed 17.6 million lives globally in 2016. Reducing premature MI and CVD is a key priority for all nations; however, there is sparse synthesis of information on risk factors associated with premature MI. To address this knowledge gap, we are conducting a systematic review to describe the association between risk factors (demographics, lifestyle factors and biomarkers) and premature MI.Methods and analysisThe following databases were searched from inception to June 2018: CENTRAL, CINAHL, Clinical Trials, EMBASE and MEDLINE. We will include original research articles (case–control, cohort and cross-sectional studies) that report a quantitative relationship between at least one risk factor and premature MI. Two investigators will use predetermined selection criteria and independently screen articles based on title and abstract (primary screening). Articles that meet selection criteria will undergo full-text screening based on criteria used for primary screening (secondary screening). Data will be extracted using predetermined data extraction forms. The Newcastle-Ottawa Scale for case–control and cohort studies will be used to evaluate the risk of bias and will be adapted for cross-sectional studies. Whenever feasible, data will be summarised into a random-effects meta-analysis.Ethics and disseminationTo our knowledge, this will be the first study to synthesise results on the relationship between risk factors and premature MI. These findings will inform healthcare providers on factors associated with risk of premature MI and potentially improve primary prevention efforts by guiding development of interventions. These findings will be summarised and presented at conferences and through publication in a peer-reviewed journal.PROSPERO registration numberCRD42018076862.