Objective: To identify and quantify current deficiencies in primary and secondary stroke prevention, as well as potential gains from optimal employment of thrombolysis. Design, participants and setting: Observational study of 259 consecutive patients admitted to a tertiary hospital stroke unit from 24 January 2006 to 10 January 2007, with retrospective assessment of prestroke risk factors and therapies to determine stroke preventability, based on relative risk reductions from published meta-analyses of preventive therapies. Main outcome measures: Numbers of strokes preventable by optimal risk factor modification and numbers of strokes with preventable disability through optimal thrombolysis; characteristics of patients with preventable strokes; contributions of each risk factor to stroke preventability. Results: 183 patients had a disabling or fatal stroke; 135 patients had at least one suboptimally managed risk factor. On the basis of prespecified stroke preventability weightings, 70 strokes were preventable. The younger the patient, the more likely that the stroke was potentially preventable (relative risk [RR] for age < 60: >= 80 years, 3.10; 95% Cl, 1.96-4.92). Smoking, inadequate control of hypertension and suboptimal anticoagulation accounted for nearly 90% of preventable strokes. Patients with target systolic blood pressures of 130 mmHg or lower were more likely to have inadequately controlled hypertension (RR, 4.27; 95% Cl, 2.58-7.05). By comparison, disability could have been prevented in four strokes through optimal thrombolysis. Conclusions: A significant proportion of stroke remains preventable, especially in younger patients, by optimal modification of risk factors, particularly smoking, blood pressure and anticoagulation. Only a small proportion of patients will benefit from best-practice thrombolysis. MJA 2009; 190: 678-682