Background Cerebral edema (CED) deteriorates outcome of ischemic stroke patients, and there is no effective medical treatment. Limited data exist on cerebral edema after stroke thrombolysis. Aims We aimed to analyze impact of cerebral edema on the outcome of thrombolysis-treated patients. Methods Our cohort included 943 thrombolysis-treated ischemic stroke patients at the Helsinki University Central Hospital (1995–2008). Cerebral edema represented focal brain swelling up to 1/3 (CED-1) or greater than 1/3 (CED-2) of the hemisphere, or midline shift (CED-3). We studied baseline parameters associated with development of cerebral edema and association of cerebral edema with three-month outcome (modified Rankin Scale, mRS). Results On control imaging, CED-1 was present in 167 (17·7%), CED-2 in 40 (4·2%), and CED-3 in 53 (5·6%) patients. Compared with patients without edema ( n = 683), patients with cerebral edema had higher baseline National Institutes of Health Stroke Scale scores, more often hyperdense cerebral artery sign or early infarct signs on admission computerized tomography, and received thrombolysis later. Cerebral edema was independently associated with poor outcome (mRS 3–6) and mortality, whereas favorable outcome (mRS 0–2) was observed in 77 (46%), 5 (13%), and 3 (6%) patients with CED 1, 2, and 3, respectively. Anti-edema treatment was considered necessary and administered to 49/260 (19%) patients; only five had favorable outcome. Conclusions Cerebral edema is frequent (28%) among thrombolysis-treated ischemic stroke patients, occurring in severe forms in 10%. Higher baseline National Institutes of Health Stroke Scale, presence of hyperdense cerebral artery sign or early infarct signs, and longer treatment delays are associated with edema development. Edema is a strong independent predictor of three-month outcome. Effect of anti-edema treatment was modest.