Coronary stent thrombosis (CST) is a major concern of interventional cardiology. Several risk factors for CST have been identified, but as a whole they do not explain the pathophysiology of CST. This study was designed to investigate whether acute infection-inflammation could facilitate the occurrence of CST. Forty-one patients, aged 66.6 +/- 11 years, consecutively admitted to our catheterization laboratory for acute, subacute or late CST, were retrospectively analysed. Transient acute infection-inflammation on admission for CST was diagnosed by predefined criteria. Prevalence of known risk factors for CST was also investigated. Twenty-one patients (51%) met predefined criteria for the occurrence of acute infection-inflammation. On admission, in these patients, levels of systemic humoral and cellular inflammatory markers were significantly higher than those of patients without recent or ongoing acute infection-inflammation (p < 0.05 for all). 62% of patients with acute infection-inflammation had less than two known risk factors for CST whereas only 37% patients without infection-inflammation showed less than two risk factors (p = 0.03) and showed more frequent interruption of antiplatelet treatment (17 vs. 2.4%, p = 0.02), mean longer stent length (20.5 +/- 4.8 vs. 16.5 +/- 5.1 mm, p = 0.02) and lower left ventricular ejection fraction before CST (42.9 +/- 14 vs. 47.3 +/- 11%, p = 0.02). In conclusion, acute infection-inflammation could play a role in facilitating the occurrence of CST in a subgroup with low risk profile for known risk factors. Our findings, if confirmed, could suggest new opportunities for prevention and treatment of CST.