The Framingham Stroke Risk Profile (FSRP) is a validated model for predicting 10-year ischemic stroke risk in middle-aged adults, yet has not been demonstrated to consistently translate in older populations. This is a systematic review of independent risk factors measured among > 65 year olds, with subsequent first ischemic stroke, using PRISMA guidelines. We appraised peer-reviewed publications that included participants > 65 years old at risk assessment. Combined with other criteria, results were abstracted from 28 papers reporting six types of stroke risk factors: Serologic/Diagnostic, Conventional, Psychosocial, Genetic, Cognitive, and Antibiotic use. These studies demonstrated levels of serum androgens, C-reactive protein, and advanced glycation endproducts; thrombin generation; left ventricular mass; depressive symptoms; phosphodiesterase 4D single nucleotide polymorphisms; coagulation factor XII gene; peak thrombus generation; and lower cognitive functioning were independent risk factors for ischemic stroke in older adults. Plasma adipokines, free fatty acids and antibiotic use did not predict ischemic stroke. Purpose in life and APOEε2 allele were protective for ischemic stroke. This systematic review provides evidence of risk and protective factors for ischemic stroke in older cohorts that are not included in the FSRP. Further studies are needed to understand whether these factors are important enough to comprise a risk score.