AIM: To compare the safety and clinical outcomes of subconjunctival trypsin and dexamethasone (DEX) injections in the treatment of anterior chamber fibrin exudates in eyes with globe rupture following primary wound repair and vitrectomy. METHODS: A retrospective analysis included 42 males and 10 females (mean age 46.0±6.0y, range 34 to 58y) who underwent primary wound sutures and vitrectomy for globe rupture. Patients with pupil-covered fibrinous exudate or/and membrane in the anterior chamber were treated. On the first postoperative day, subconjunctival injections of either 5000 units (0.4 mL) of trypsin solution (n=25) or 0.5 mL (1 mg) DEX (n=27) were administered to accelerate exudate absorption. Efficacy was assessed by observing break time and partial absorption of the fibrin exudate membrane. Safety and comfort were evaluated by monitoring intraocular pressure (IOP), allergy, pain, and foreign body sensation. RESULTS: Both groups achieved 1/3 absorption of the anterior chamber fibrin exudate membrane, but the trypsin group exhibited shorter break time and partial absorption time compared to the DEX group (P<0.05). Trypsin treatment was also less irritating to patients. No adverse reactions were reported, and IOP remained stable. Visual acuity improved in both groups without statistical difference. CONCLUSION: Compared to DEX, trypsin demonstrates a shorter absorption time for the fibrin exudate membrane with a more comfortable process in treating pupil-covered fibrinous exudate or/and membrane after vitrectomy for globe rupture.