Purpose The efficacy and adverse effects of 0.25% apraclonidine on intraocular pressure (IOP) after Nd: YAG laser posterior capsulotomy were investigated, and the results were compared with placebo, 0.50% timolol maleate and 1% apraclonidine. Methods Eighty eyes were randomly assigned to four groups of 20 eyes. In a double-masked design, the groups were treated with placebo (group I), 0.50% timolol maleate (group 2), 1% apraclonidine (group 3), 0.25% apraclonidine (group 4) one hour before and five minutes after Nd:YAG laser posterior capsulotomy. IOP was measured by applanation tonometry 1 hour before (baseline IOP) and 1,3, 24 hours after capsulotomy. Results The average baseline IOP increased respectively 3.90 ± 5.35, 5.95 ± 5.32, 1.15 ± 3.20 mmHg in the first group 1, 3 and 24 hours post-treatment. There were significant differences between baseline IOP and 1 and 3 hours but not at 24 hours (p=0.004, p=0.001, p=0.13). IOP increased 0.40 ± 4.08, 0.75 ± 5.33, 0.80 ± 6.03 mmHg in the second group at the same times. The differences between the average baseline IOP and the 1, 3 and 24h measurement were not significant (p=0.83, p=0.65, p=0.93). In the third group, IOP decreased 3.70 ± 2.40, 3.30 ± 2.47, 2.65 ± 1.56 mmHg at the measurement times, with significant differences between the average baseline IOP and the 1, 3 and 24 hour measurements (p=0.001, p=0.0001, p=0.01). In the fourth group IOP increased 0.35 ± 3.32 mmHg at 1 hour, but decreased 1.25 ± 3.41, 0.90 ± 2.07 mmHg at 3 and 24 hours. The differences were not significant (p=0.94, p=0.16, p=0.08). When the 0.25% and 1% apraclonidine groups were compared, there were significant differences between the average IOP at 1 hour in both groups but not at 3 and 24 hours (p=0.01, p=0.17, p=0.21). Similarly, there were no significant differences between the average IOP at the same times when the 0.25% apraclonidine group was compared with the timolol group (p=0.30, p=0.08, p=0.16). Some systemic and local side effects were seen in the timolol and 1% apraclonidine groups, but none with 0.25% apraclonidine. Conclusions It was concluded that 0.25% apraclonidine is effective in preventing the early elevation of IOP after Nd:YAG laser posterior capsulotomy and may offer an alternative to 0.50% timolol maleate and 1% apraclonidine.