Background/aim: To compare the effectiveness of intraoperative 5 fluorouracil (5-FU) and mitomycin C (MMC) application in preventing recurrence following primary pterygium excision. Materials and methods: This was a prospective clinical trial that included 93 patients with primary pterygia assigned to three treatment groups in which 29 patients received an intraoperative application of 25 mg/mL 5-FU for 5 min, 32 patients received an intraoperative application of 0.02% MMC for 5 min, and 32 patients underwent only surgical excision (the control group). Follow-up visits were done on postoperative days 1, 3, 7, 15, and 30, and then every month. Results: After a mean follow-up of 14 months, the surgical excision recurrence rates in the 5-FU, MMC, and control groups were 27.6%, 12.5%, and 43.75%, respectively. There was a statistically significant difference in the 5-FU and MMC groups when compared with the control group (chi-square; P = 0.04); however, the difference between the 5-FU and MMC groups was not significant. No serious complications were seen in the 5-FU and MMC groups. Conclusion: Intraoperative application of MMC and 5-FU is effective and safe for the prevention of recurrence. Our findings suggest that MMC is more potent for the prevention of recurrence and it causes less complaints than 5-FU.