Ocular surface squamous neoplasia (OSSN) comprises a range of dysplasia including corneal-conjunctival intraepithelial neoplasia and invasive squamous cell carcinoma. The traditional treatment for localised non-invasive OSSN has been surgical excision with or without intraoperative cryotherapy. Postoperative adjunctive topical chemotherapy significantly reduces the rate of recurrence. This paper presented a long-term follow-up of two prospective non-comparative interventional case series examining recurrence and side-effect rates in patients receiving 5-FU (fluorouracil) or mitomycin C (MMC) as adjuvants to surgical excision of localised OSSN. Eighty-nine eyes were included in the 5-FU group and 64 eyes were included in the MMC group. All patients underwent complete superficial dissection of the lesion with a 2mm margin. All lesions in the 5-FU group had cryotherapy applied intraoperatively, however, cryotherapy was not available in 18.7% of cases in the MMC arm. Median follow-up was 33.6 months in the 5-FU arm and 57.9 months in the MMC arm. There were no recurrences in the MMC arm and one recurrence in the 5-FU arm. This case of recurrence was in an incompletely excised CIN III lesion with an incomplete course of adjuvant 5-FU therapy. Overall, side-effects were encountered in 69% of 5-FU cases compared with 41% of MMC cases. Sixty-two percent of 5-FU cases experienced lid toxicity vs. 0% of MMC cases. No 5-FU cases experienced allergy vs. 28% of MMC cases. Ten percent of patients in the 5-FU group developed epiphora, compared with 17% in the MMC group. The authors concluded that recurrence is rare when adjuvant 5-FU or MMC is used in surgically excised localised OSSN and although side-effects are common, the majority are transient and rarely limit compliance.