Background: The aim of this study was to compare the outcomes after subretinal recombinant tissue plasminogen activator (rtPA) treatment for subretinal hemorrhages (SRH), subpigment epithelial hemorrhages (SPH), and combined subretinal and subpigment epithelial hemorrhages (CH). Methods: An observational analysis of patients treated with subretinal rtPA was performed. The primary endpoint was the assessment of visual improvement (best-corrected visual acuity, BCVA) after surgery. Secondary endpoints were evaluation of the maximal hemorrhage diameter (MHD) and central macular thickness (CMT) measured by spectral domain optical coherence tomography. Results: From a total of 83 eyes included in the study, 19 eyes showed SRH, 11 eyes SPH, and 53 eyes CH. For SRH and CH, the mean BCVA, MHD, and CMT improved significantly (p < 0.05). For patients with SPH, both the mean MHD and CMT decreased significantly (p < 0.05), whereas the mean BCVA improved only slightly after surgery (p = 0.28). Conclusion: Vitrectomy combined with subretinal rtPA injection and gas or air tamponade has a strong functional and anatomical effect on both SRH and CH and also seems to slightly improve the anatomical outcome in SPH.