A unique extant database to explain heterogeneity in peripheral immune response (PIR) over time in response to stroke/transient ischemic attack (TIA) was used to compare changes in PIR between first-time and recurrent stroke/TIA and to identify distinct and common trajectories of change in the PIR in stroke/TIA. Associations between risk factors for stroke (hypertension, smoking, diabetes, hypercholesterolemia, infection) and PIR trajectory were quantified using multivariate random effects modeling. With comparable admission values, patients with recurrent stroke/TIA had a persistent elevation in lymphocyte percentage as opposed to the significant decline in lymphocyte percentages over time observed in those with first-time stroke/TIA. Two naturally occurring trajectories of the PIR to stroke/TIA were observed, one indicative of a primed PIR and one indicative of an unprimed PIR. A large proportion of the sample, 80%, was classified as having persistently higher lymphocyte percentages and lower neutrophil percentages over time compared with the remainder of the sample. When controlling for risk factors for stroke, adults admitted with recurrent stroke/TIA without infection were more than three times as likely to have a primed PIR (i.e., the high lymphocyte-low neutrophil trajectory) than those with first-time stroke with infection. Interventions for reduction of neurological deficits require tight implementation windows early after stroke occurs. The outlined classification of cases in these primed and unprimed trajectories of the PIR adds to the knowledge of optimal clinical timing for de novo immune-based interventions.