AIM: To evaluate whether the level of thrombospondin-1 (TSP-1) in aqueous humor can predict the prognosis of trabeculectomy in patients with primary angle-closure glaucoma (PACG). METHODS: This case-control study involved 26 patients with PACG who experienced a failed trabeculectomy (case group) and 78 age- and sex-matched patients with PACG who underwent successful trabeculectomy (control group). Aqueous humor was collected at the time of trabeculectomy and tested for TSP-1 and TGF-β2 levels with an enzyme-linked immunosorbent assay method. Logistic regression modeling was used to assess the risk factors for failed trabeculectomy. RESULTS: The mean TSP-1 aqueous concentrations were significantly higher in the case group (20.67±9.79 ng/mL) than the control group (5.17±2.29 ng/mL) (P<0.001). The transforming growth factor-β2 (TGF-β2) aqueous concentrations were significantly different between the case and control group, at 3633.25 and 1090.24 pg/mL, respectively (P<0.001). Logistic regression analysis revealed TSP-1 level as an independent risk factor for a failed trabeculectomy (OR=3.540; 95%CI=1.092-11.482). CONCLUSION: The aqueous humor TSP-1 and TGF-β2 levels are higher in PACG eyes with failed trabeculectomy than with successful trabeculectomy at one year. The aqueous humor TSP-1 level is an independent risk factor associated with failed trabeculectomy.