Intravenous thrombolysis (IVT) is an established treatment in patients suffering from acute ischemic stroke (AIS). IVT might increase the risk of postoperative complications if applied prior to decompressive craniectomy (DC). Therefore, we analyzed the management of patients with and without IVT prior to DC. Between 1999 and 2011, DC was performed in 115 patients after AIS. Patients with and without IVT prior to DC were compared regarding perioperative management, postoperative complications and outcome. Postoperative complications were stratified into non-bleeding and bleeding complications. Outcome was assessed using the modified Rankin scale after three months. Two multivariate analyses were performed to identify predictors for postoperative complications and predictors for unfavourable outcome (mRS 4-6). Fifty-two of 115 patients underwent IVT prior to DC (45 %). Forty-four patients were on antiplatelet therapy prior to DC (38 %). Frequency of bleeding complications did not differ significantly in patients with IVT prior to DC compared to patients without. However, bleeding complications occurred significantly more often in patients with antiplatelet use prior to DC (p = 0.0003, OR 4.5). In the multivariate analysis "preoperative use of acetylsalicylic acid" was the only independent predictor associated with bleeding complications (p = 0.002, OR 3.9). IVT prior to DC did not predict unfavourable outcome. There was no evidence in this observational study that IVT prior to DC places patients at undue risk of bleeding complications after subsequent DC. Patients with or without IVT prior to DC suffered significantly more often from postoperative bleeding complications if antiplatelet therapy was applied before onset of AIS.