The postoperative course after cataract surgery can be complicated by the formation of severe fibrinous membranes, especially in cases with previous goniotrepanation, after syn echiolysis, iridotomy or iris suturing, and in patients with diabetes or uveitis. This study retrospectively analyzes the efficacy of intraocular tissue plasminogen activator (tPA) for fibrinolysis in these conditions commonly considered as contraindications to tPA therapy. When antiinflammatory therapy was unsuccessful in lysing fibrinous membranes, 10 micrograms of tPA (Actilyse) was injected into the anterior chamber following the first postoperative day (n = 15). In addition, topical corticosteroids and cycloplegics were given postoperatively. Lysis of the fibrinous membranes was achieved in all patients. However, in three cases lysis was incomplete or recurred. Complications of intraocular tPA therapy consisted of mild hyphema (n = 1) and transient dysfunction of the corneal endothelial cells (n = 2). In conclusion, the results suggest intraocular low-dose tPA as an effective approach for the treatment of severe fibrinous membranes after cataract surgery even in high-risk patients.