BACKGROUND Postoperative recurrence of pterygium occurs in many patients. The authors studied the recurrence rate of pterygium after administration of a single intraoperative dosage of topcial mitomycin C at the completion of pterygium excision. METHODS Eighty-one patients underwent excision of the pterygium, leaving the sclera bare. The first 60 patients were randomized into two treatment groups of 30 patients each. Their remaining 21 patients were offered mitomycin C. Group 1 included 49 patients (30 randomized and 19 of the remaining 21 patients) who received an intraoperative application of 0.02% (0.2 mg/ml) mitomycin C for 5 minutes, and group 2 included 32 patients (30 randomized and 2 of the remaining 21 patients) who received NaCl 0.9% instead of mitomycin C. Patients were followed from 12 to 28 months in a masked manner. RESULTS The pterygium recurred in 2 (4%) of 49 patients in group 1 and in 15 (46.7%) of the 32 patients in group 2 (P = 0.0001). A delay of epithelialization for 5 and 10 weeks occurred in two patients in group 2 and granuloma manifested in one patient in group 1. CONCLUSIONS This study indicates that intraoperative administration of a single dosage of 0.02% mitomycin C is an effective treatment for prevention of recurrence of pterygium.