OBJECTIVES: To investigate the association between use of typical and atypical antipsychotic drugs and incidence of stroke in patients with and without dementia. DESIGN: Self controlled case series. SETTING: UK based electronic primary care records in the general practice research database (GPRD). PARTICIPANTS: All patients registered in the database with a recorded incident stroke and at least one prescription for any antipsychotic drug before the end of 2002: 6790 eligible participants were identified and included in the final analysis. MAIN OUTCOME MEASURES: Rate ratio for stroke in periods of time exposed to antipsychotics compared with unexposed periods. RESULTS: Use of any antipsychotic drug was associated with a rate ratio for stroke of 1.73 (95% confidence interval 1.60 to 1.87): 1.69 (1.55 to 1.84) for typical antipsychotics and 2.32 (1.73 to 3.10) for atypical antipsychotics. In patients receiving any antipsychotic drug, the rate ratios were 3.50 (2.97 to 4.12) for those with dementia and 1.41 (1.29 to 1.55) for those without dementia. CONCLUSIONS: All antipsychotics are associated with an increased risk of stroke, and the risk might be higher in patients receiving atypical antipsychotics than those receiving typical antipsychotics. People with dementia seem to be at a higher risk of an associated stroke than people without dementia and use of antipsychotics should, when possible, be avoided in these patients.