Activated protein C resistance (APC-R) is the most common inherited cause of clinically apparent venous thromboembolism. Previous data indicate that left atrial thrombus (LAT) formation is a common complication in mitral stenosis (MS) and a hypercoagulable state exists in these patients. The aim of this study was to invastigate the association between APC-R and LAT formation in patients with MS. Seventy-seven consecutive patients with rheumatic MS were included in this study. Transesophageal echocardiography was performed on all patients to assess the presence of any thrombus or spontaneous echo contrast (LASEC) in the left atrial cavity or appendage. Thirty four of the patients had LAT and 43 did not. Prevelance of APC-R was smiliar between the two groups of patients with and without LAT (23% vs 16%, p=0.425). LAT(+) patients had higher incidence of atrial fibrillation (AF, 74% vs 51%, p=0.046) and LASEC (71% vs 19%, p<0.001) compared to LAT(-) patients. On multivariate regression analysis, only the presence of LASEC achieved statistical significance as an independent risk factor for LAT formation (p=0.0001, odds ratio=9.589, 95% confidence interval [CI]=3.143-29.251). Because on univariate analysis both LASEC and AF were associated with LAT, we also compared the prevelance of APC-R in the subgroups of patients who have these risk factors with and without LAT. There was a correlation between the presence of APC-R and LAT in the AF(+) subgroup of MS patients (p=0.033, odds ratio=8.167, 95% CI=1.001-72.812). However, the presence of APC-R was not associated with the increased risk of LAT in LASEC(+) patients (p=0.217, odds ratio=1.200, 95% CI=1.003-1.435). Although the presence of APC-R itself is not an independent risk factor for LAT formation in MS, it may increase the risk of LAT when present in combination with AF (as an additional risk factor) in these patients.