OBJECTIVE: To determine whether a single topical aqueous suppressant applied immediately after pars plana vitrectomy with long-acting gas tamponade prevents intraocular pressure (IOP) elevation. METHODS: Fifty patients who met the inclusion criteria and underwent pars plana vitrectomy with long-acting gas tamponade were randomized to receive a combination of timolol maleate and dorzolamide hydrochloride, long-acting timolol alone, dorzolamide alone, or placebo at the conclusion of surgery. The IOP was checked by a portable, handheld tonometer (Tono-Pen) at the conclusion of surgery and at 5 hours, 1 day, and 1 week after surgery. RESULTS: There were no significant differences in IOP among the groups at the conclusion of surgery. The IOP at 5 hours after surgery (27.0 vs 17.4 mm Hg; P<.001) and 1 day after surgery (26.1 vs 19.9 mm Hg; P =.01) showed a statistically significant difference between the placebo and timolol-dorzolamide groups. The timolol-dorzolamide group showed greater IOP control than either the timolol alone or the dorzolamide alone groups at 5 hours (P =.04 for both). CONCLUSION: The use of a single topical aqueous suppressant (timolol-dorzolamide) given after pars plana vitrectomy with long-acting gas tamponade effectively prevents significant postoperative IOP elevation at 5 hours and 1 day after surgery.