Objectives. To assess the prevalence of activated protein C resistance (APC‐R) among healthy subjects and thromboembolic patients and to determine the clinical characteristics associated with APC‐R. Design. A prospective study. Setting. One academic medical centre. Subjects. 91 health controls and 126 thromboembolic patients. Measurements. Patients and control were genotyped for the factor V Leiden (VaQ506) mutation. The anticoagulant response of the patient's plasma to activated protein C was also determined. Results. The frequency of APC‐R was 3.3% among healthy control subjects and 22% among thrombotic patients of whom 18% were heterozygous and 4% were homozygous. The mean age at the first thrombotic event and the severity of thrombotic disease including the proportion of proximal deep vein thrombosis and the frequency of lung embolism were identical among APC‐R positive and negative patients. A family history of thromboembolic disease was elicited more frequently in APC‐R positive than in APC‐R negative patients (57% vs. 22%, P <0.001). The recurrence rate was higher for APCR‐R positive patients (57% vs. 34%, P <0.05). The percentage of cases with a factor predisposing to thrombosis was very similar in APC‐R positive (57%) and negative (68%) patients. Conclusions. A familial history of thromboembolic disease and recurrences are significantly more frequent among APC‐R positive than APC‐R negative patients.