Although short activated partial thromboplastin times (APTTs) are generally considered to be laboratory artefacts of problematic blood collections, there is mounting evidence that in some cases a short APTT may reflect a hypercoagulable state, potentially associated with increased thrombotic risk and adverse cardiovascular events. We prospectively evaluated the phenomenon of short APTTs in 113 consecutive samples compared with an equal number of age and sex-matched normal APTT samples. We found a significant difference in various test parameters including prothrombin time (PT), Factor (F) V, FVIII, FXI, FXII, von Willebrand factor (VWF) antigen and collagen-binding activity, and in the level of procoagulant phospholipids, as assessed using a novel assay procedure (XACT). Interestingly, there was a significant negative association for fibrinogen, and although elevated, there was no significant association for FIX. On the basis of identified consecutive samples having multiple low APTTs on several sequential days, a proportion of laboratory-defined short APTTs appear to represent in-vivo hypercoagulability. In conclusion, plasma from patients presenting with short APTTs is reflective of a complex hypercoagulant milieu that could feasibly contribute to thrombotic risk, and 20% or more of laboratory definable short APTTs appear to reflect in-vivo phenomenon.