Purpose To compare the anatomic and functional outcomes of treating thick submacular haemorrhage with intravitreal gas injection with and without tissue plasminogen activator (t-PA) in patients with age-related macular degeneration. Methods A review of age-related macular degeneration patients with submacular haemorrhage who underwent intravitreal gas injection with and without t-PA at a tertiary referral centre was conducted. Main outcome measures were best and final postoperative visual acuity. Results A total of 53 eyes of 53 patients were included, 28 eyes received intravitreal t-PA and gas injection (t-PA and gas group) and 25 eyes received intravitreal gas injection alone (gas-alone group). Incidence of best visual acuity improvement was significantly higher in the t-PA and gas group than in the gas-alone group (60.7 vs 32.0%; P ¼ 0.037). However, subgroup analysis demonstrated that the difference was significant only in eyes with haemorrhage duration of more than 14 days (46.2 vs 8.3%; P ¼ 0.035). Incidence of final visual acuity improvement was not significantly different between the two groups (42.9 vs 28.0%; P ¼ 0.39). The complications of vitreous haemorrhage and endophthalmitis were similar between the two groups. Multiple logistic regression analysis demonstrated that shorter haemorrhage duration (o14 days) was the main factor predictive of best visual acuity improvement (OR ¼ 9.02, P ¼ 0.015). Whether t-PA was used was of borderline significance (OR ¼ 4.96, P ¼ 0.046). AbstractConclusions Intravitreal t-PA was valuable for submacular haemorrhage only in eyes with relatively old haemorrhage. For eyes with recent onset of haemorrhage, t-PA is suggested only if initial gas injection failed to displace submacular haemorrhage.