OBJECTIVE To determine the effect of preinjection ocular decompression by cotton swabs on the immediate rise in intraocular pressure (IOP) after intravitreal injections. METHODS Forty-eight patients receiving 0.05 mL ranibizumab injections in a retina clinic were randomized to 2 anesthetic methods in each eye on the same day (if bilateral disease) or on consecutive visits (if unilateral disease). One method utilized cotton swabs soaked in 4% lidocaine applied to the globe with moderate pressure and the other 3.5% lidocaine gel applied without pressure. IOPs were recorded at baseline (before injection) and at 0, 5, 10, and 15 minutes after the injection until the IOP was ≤30 mm Hg. The IOP elevations from baseline were compared after the 2 anesthetic methods. RESULTS The preinjection mean IOP (SD, mm Hg) was 15.5 (3.3) before the cotton swabs and 15.9 (3.0) before the gel (P=0.28). Mean IOP (SD, mm Hg) change immediately after injection was 25.7 (9.2) after the cotton swabs and 30.9 (9.9) after the gel (P=0.001). Thirty-five percent of gel eyes had IOP≥50 mm Hg compared with only 10% of cotton swab eyes immediately after the injection (P<0.001). CONCLUSION Decompressing the eye with cotton swabs during anesthetic preparation before an intravitreal injection produces a significantly lower IOP spike after the injection.