Purpose: To describe the intraocular pressure (IOP)-lowering effects in eyes with open-angle glaucoma (OAG) after treatment with an anterior juxtascleral depot of anecortave acetate. Design: Prospective, interventional case series. Methods: Seven eyes of six subjects with OAG, with uncontrolled IOP while being administered one or more topical medications, received 24 mg anecortave acetate delivered by anterior juxtascleral depot. IOP was assessed at baseline and regularly after treatment for up to 24 months. Results: Mean IOP before anecortave acetate treatment was 31.3 ± 11.3 mm Hg and dropped by 9.5 ± 4.5 mm Hg (32.7% ± 16.8%) within one week after treatment. This IOP reduction was sustained through six months (8.4 ± 5.4 mm Hg [29.6% ± 12.4%]) and 12 months (9.5 ± 5.7 mm Hg [34.0% ± 15.9%]) after a single anecortave acetate treatment. The injection process was well tolerated, and no eyes experienced any injection-related or drug-related serious adverse events. Conclusions: Both the anterior juxtascleral depot of a drug and anecortave acetate may be promising candidates for IOP reduction in eyes with OAG. Additional studies are required to establish better their efficacy and safety, optimal dosing frequency, mechanism of action, and potential additivity to other IOP-lowering therapies.