OBJECTIVES: Previous stroke risk equations identified systolic blood pressure (SBP) as a key predictive factor. Recent evidence suggests that pulse pressure (PP), defined as the difference between SBP and diastolic blood pressure, could be a new risk factor. This project aims at developing and validating a new stroke risk equation incorporating PP as a potential risk factor. METHODS: Electronic medical records including laboratory data of a random sample of 97,237 hypertensive patients from a US integrated health delivery system were analyzed (01/2004-05/2012).  Patients with ≥1 peripheral PP (PPP) reading and ≥6 months of observation (baseline period) prior to the first evidence of hypertension were randomly split into the development (two-thirds of sample) and validation (one-third of sample) datasets. Stroke events were identified using ICD-9-CM 433.xx-436.xx. Cox proportional hazards models assessed time to first stroke event based on baseline risk factors, including PPP, age, gender, SBP, smoking status, BMI, diabetes, and cardiac comorbidities. The optimal risk equation was selected using the least absolute shrinkage and selection operator (LASSO); performance was evaluated by the c-statistic. RESULTS: 30,525 patients without stroke (mean age 58.2, 48% male) and 4,272 patients with stroke (mean age 67.3, 48% male) were selected. Average observation was 3.89 years. PPP was higher among patients who developed stroke (mean [SD] PPP, stroke: 62.0 [15.3] mmHg; non-stroke: 58.1 [14.0] mmHg, p<.001). The best performing risk equation (c-statistic, development: 0.732; validation: 0.722) included PPP (hazard ratio per 10 mmHg increase: 1.0676, p<.001) as a significant risk factor for stroke in addition to age and diabetes, among others. CONCLUSIONS: This stroke risk equation shows that greater PP is a significant predictive factor for increased stroke risk, even in the presence of known risk factors, including SBP. PP should be considered by practitioners along with traditional risk factors in treatment strategies to prevent stroke.