Purpose: To describe the authors' clinical experience with intracameral tissue plasminogen activator (tPA) after glaucoma surgery. Methods: Retrospective review of medical records of all patients who received intracameral tPA after glaucoma surgery at the Doheny Eye Institute from November 4, 1992, to June 14, 1994. There were 20 tPA administrations (18 eyes of 17 patients) in doses ranging from 6 to 25 μg. Indication for tPA administration was decreased bleb function secondary to blood/fibrin clot in aqueous outflow pathway. Results: Tissue plasminogen activator was given after trabeculectomy (5 drug administrations) and combined cataract extraction/trabeculectomy procedures (9 drug administrations), with increased filtration in 12 (86%). There were five (36%) instances of hyphema and three (21%) of hypotony. All hyphemas occurred after doses of 25 μg. Final IOP of 18 mmHg or lower and 6 mmHg or higher was achieved in 11 (92%) of 12 patients after a mean follow-up interval of 4.2 ± 4.7 months. The six remaining tPA irrigations were done in five patients after glaucoma drainage implant surgery (n = 4) or surgical/needle revision of a filtering bleb (n = 2). Conclusions: Aqueous outflow obstruction from blood/fibrin clot after glaucoma surgery may be treated effectively with intracameral tPA in doses of 6 to 25 μg. The authors recommend using a dose of less than or equal to 6 to 12.5 μg to minimize the risk of hyphema.