Abstract Introduction Myocardial infarction (MI) with (MI-CAD) and without (MINOCA) obstructive coronary artery disease affects different populations and may have separate pathophysiological mechanisms with greater inflammatory activity in MINOCA compared to MI-CAD. Helicobacter pylori (Hp) is the most common chronic infection globally. It can cause systemic inflammation and has been associated with cardiovascular disease (CVD). We aimed to investigate whether Hp infection is associated with concentrations of protein biomarkers of inflammation and CVD. Methods In a case-control study patients with MINOCA (n=99) in Sweden were included, complemented by subjects with MI-CAD (n=99) and controls (n=100) matched by age and sex. Protein biomarkers were measured with a proximity extension assay in plasma samples collected 3 months after MI. Seroprevalence of Hp and cytotoxin associated gene A (CagA) was determined using ELISA. The associations between protein levels and Hp status were studied with linear regression. Results The prevalence of Hp was 20.2%, 19.2% and 16.0% for MINOCA, MI-CAD and controls, respectively (p=0.73). Seven proteins were significantly associated with Hp in an adjusted model: tissue plasminogen activator (tPA), interleukin-6 (IL-6), myeloperoxidase (MPO), TNF-related activation-induced cytokine (TRANCE), pappalysin-1 (PAPPA), soluble urokinase plasminogen activator receptor (suPAR) and P-selectin glycoprotein ligand 1 (PSGL-1). Conclusion Hp infection was present in one in five patients with MI, irrespective of the presence of obstructive CAD. Proteins previously associated with MINOCA and MI-CAD were elevated in Hp positive subjects, suggesting that Hp might promote an inflammatory response and contribute to the development of MI with and without CAD.Forest plot of regression coefficients