Recent post-marketing surveillance reports have confirmed the benign safety profile and lack of organ toxicity shown by piracetam during its 25 years of clinical usage. Tolerance has proved equally good with the more recent use of larger doses (up to 24 g/day) for the long-term control of cortical myoclonus and when given intravenously to patients with acute stroke. This paper provides a brief review of these findings and records the safety of piracetam as found in the Piracetam in Acute Stroke Study (PASS), a randomized multicenter placebo-controlled study in 927 patients with acute ischemic stroke. Patients receive one intravenous bolus injection of placebo or 12 g piracetam, piracetam 12 g daily for 4 weeks and maintenance treatment for 8 weeks. The major results have been reported (De Deyn et al., Stroke 28  2347-2352). Safety was assessed taking into account adverse events including abnormal laboratory test results and mortality. Death within 12 weeks occurred more frequently in the piracetam group but the difference from placebo was not significant. Of many potential risk, prognostic and treatment-related factors examined by logistic regression, 6 contributed significantly to death of which the most important were initial severity of stroke and age. Neither treatment nor any treatment-related factor contributed significantly to death. Adverse events were similar in frequency, type and severity in piracetam and placebo groups. Events of cerebral, non-cerebral and uncertain origin likewise occurred with similar frequency. Few patients discontinued because of adverse events. There was no difference between treatments in the frequency of events associated with bleeding, including hemorrhagic transformation of infarction. An important finding was that, of 31 patients with primary hemorrhagic stroke enrolled, 3 piracetam-treated patients died compared with 6 on placebo. The results suggest that piracetam in high dosage may be given to patients with acute stroke without significant adverse effects.