Purpose The perfect intravitreal injection delivers an exact amount of medication with the least risk to vision and the eye. We examined 2 different methods of intravitreal injection to determine if an angled transscleral entry for intravitreal injection results in less egress of intravitreal contents, including medication. Methods In a crossover controlled trial at an outpatient clinical facility within a major ophthalmology referral center, we treated 10 patients. The surgical technique involved injecting 0.05 mL of bevacizumab injected in one eye by both an orthogonal (straight in) and oblique (angled) technique. The intraocular pressure (IOP) was measured immediately before and after each monthly injection. Results Orthogonal injections raised the IOP significantly less (mean 24.6 mm Hg or 126%) than oblique injections (29.6 mm Hg or 152%) (p = 0.045). There were no reported differences in injection-related pain or adverse effects between the techniques. Conclusions Oblique or angled injections caused a larger IOP rise than straight or orthogonal injections. This finding suggests that oblique injections are self-sealing, deliver a higher dose of medication, or prevent vitreous reflux as well as close a potential portal of entry for pathogens.