Objectives Comparison of two minimally invasive procedures for the treatment of intracerebral hemorrhage and subsequent lysis with regard to technical implications and clinical outcome of the patients. Methods Retrospective analysis of 126 patients with spontaneous supratentorial intracerebral hemorrhage treated by frame-based (n=53) or frameless (n=75) hematoma aspiration and subsequent fibrinolysis with recombinant tissue plasminogen activator (rt-PA). Data were analysed for the whole group as well as for the two subsets of patients with regard to hematoma reduction, procedure-related complications, and the early and long term clinical outcome of the patients. Functional outcome was rated using the Glasgow Outcome Scale (GOS) and Barthel-Index (median follow-up 178 weeks). The prognostic impact of patient related covariates on the GOS was analysed using logistic regression analysis. Results 49 out of 126 patients (38.9 %) died, 25 of them in the early postoperative period. Only 22/126 (17.5 %) had a favorable long term outcome (GOS >3). Age >65 years was significantly (p<0.03, OR 3.6) associated with a higher risk for an unfavorable long term outcome (GOS <= 3). Treatment had no impact on outcome. Both techniques were highly effective in reducing the intracerebral blood volume by 75.8 +/- 21.4% of the initial hematoma volume in frame-based and 64.8 +/- 25.4 % in frameless stereotaxy within 2 days of rt-PA-therapy. Malpositioning of the catheter occurred more often in the frameless group (21.3% vs. 9.4 % in the frame-based procedure) without gaining statistical significance. Conclusions Frame-based and frameless stereotactic hematoma aspirations with subsequent fibrinolysis are effective in volume reduction of intracerebral hemorrhage with comparable clinical outcome. The frameless procedure is associated with a higher risk for malpositioning of the catheter. Despite effective hematoma reduction with both techniques, the percentage of patients with a good clinical outcome remained limited especially in the elder subpopulation.