. Purpose:  To investigate how prophylactic anterior chamber paracentesis affects the intraocular pressure (IOP) after intravitreal pegaptanib injections. Methods:  In this prospective study, 41 eyes of 41 patients receiving intravitreal pegaptanib injections were randomly assigned either to receive anterior chamber paracentesis prior to the injection (Group A, 20 patients, n = 35 injections) or not (Group B, 21 patients, n = 38 injections). IOP was measured before the pegaptanib injection (T0) and 2 min (T1), 30 min (T2) and 1 week (T3) after the injection. A four‐point scale was used to evaluate the subjective pain experienced during the procedure. Results:  The mean IOP at T1 was 15.3 ± 7.5 mmHg in group A and 47.1 ± 24.1 mmHg in group B (difference −31.85 mmHg, 95% Confidence interval −40.13 to −23.56; p < 0.0001). In 45% of the injections without paracentesis, IOP was higher than 50 mmHg 2 min after the pegaptanib injection. No significant difference in IOP was observed at T0, T2 and T3 between the two study groups. The mean pain scores did not differ significantly (0.97 in group A versus 1.32 in group B; p = 0.08). Conclusions:  The results suggest that prophylactic anterior chamber paracentesis helps to prevent the high postoperative IOP spike without causing patients any additional pain.