A randomized, prospective, double-masked study was undertaken to determine the risk of postcycloplegic intraocular pressure spikes in patients with open-angle glaucoma and to evaluate apraclonidine prophylaxis in minimizing these spikes. Patients were stratified as miotic treated or untreated and each group was randomized to receive either placebo (artificial tears) or apraclonidine in both eyes before instillation of tropicamide. In both the miotic treated and untreated groups that received placebo, there was a high incidence, (37% and 38%, respectively) of clinically significant (greater than or equal to 6 mmHg) intraocular pressure spikes after instillation of tropicamide. In both the miotic treated and untreated groups, there was a statistically significant difference in postcycloplegic intraocular pressure between the subgroup that received placebo and the group that received apraclonidine prophylaxis (P = 0.003 and P = 0.006, respectively). Additionally, four eyes that received placebo had a spike of over 10 mmHg (range, 12 to 27 mmHg), while only one eye had an increase of greater than 10 mmHg (12 mmHg) in the apraclonidine group. Thus, apraclonidine appears to be a useful agent for minimizing precipitous increases in intraocular pressure after cycloplegia in eyes of open-angle glaucoma patients prone to this complication of cycloplegia.