This study aims to evaluate the effectiveness of different decompressive injection techniques in reducing intraocular pressure (IOP) spikes, if compared to the injection without pressure applied on the eye, following the intravitreal injection of bevacizumab. Patients and Methods: Two hundred patients with indication to intravitreal therapy were randomized into five arms: 40 received intravitreal injection without ocular decompression (arm A), 40 with pre-injection scleral indentation with cotton swab (arm B), 40 with preinjection digital ocular massage (arm C), 40 with post-injection scleral indentation with cotton swab (arm D) and 40 with post-injection digital ocular massage (arm E). All patients underwent measurement of the IOP with Goldamm applanation tonometer 10 minutes before and 10 minutes after the injection. The primary endpoint of the study was variation of the post-injection IOP with the different techniques. Results: An increase in post-injection IOP was observed in all the arms, if compared to preinjection values. The greatest increase was observed in arm A with a mean IOP rise of 17.60 mmHg. All other techniques showed lower mean IOP increases: arm B 10.76 mmHg, arm C 9.35 mmHg, arm D 8.8 mmHg, arm E 3.4 mmHg. The post-injection IOP differences of innovative techniques compared to the technique without ocular decompression were all statistically significant (p-value <0.01). If compared to arm A (35%), a reduction in IOP spike ≥40 mmHg frequency was also observed. The status of phakia/pseudophakia, a previous diagnosis of glaucoma and the underlying pathology for which indication was given to inject bevacizumab did not significantly alter the post-injection IOP in any of the protocols. Conclusion: The introduction of new injection protocols, such as injections performed before or after decompressive treatments, could be a safe and effective approach to control post-injection IOP increase.