Abstract--Reduced impact of ischemia after an initial ischemic insult--ischemic preconditioning--has been demonstrated in a number of animal models. Transient ischemic attack (TIA) may produce ischemic preconditioning in people who have a subsequent stroke within days of an initial ischemic insult. We performed a cohort study of all 1707 patients given a diagnosis of TIA by an emergency department physician in 1 of 16 hospitals in a managed care plan in Northern California from March 1997 to February 1998. We evaluated the impact of the timing and duration of TIA on disability in a cohort of 180 patients with TIA and subsequent ischemic stroke within 90 days of the TIA. There was no association between duration of TIA, used as a surrogate for degree of ischemia, and likelihood of disability from a subsequent stroke. Furthermore, there was no difference in rates of disability among patients with strokes occurring within 1 day, 1 to <7 days, and 7 to 90 days after the TIA. We cannot confirm results of several other studies showing an association of prior TIA with lesser stroke severity. Whether differences in underlying pathophysiology and treatment of those with prior TIA could account for differences in outcome of subsequent strokes in prior studies is unknown. Evaluating whether ischemic preconditioning occurs after TIA is extremely difficult in observational studies in humans. Given the potential hazards of inducing therapeutic transient brain ischemia in humans, a trial may not be advisable, and proof may require testing of agents that safely mimic the effects of ischemia.