We evaluated the efficacy and safety of 0.1% indomethacin and 0.1% diclofenac solutions, in controlling pain post excimer laser photorefractive keratectomy (PRK). After written consent, 61 informed patients (23 males, 38 females; mean age = 33.5 +/- 8.4 yrs) were enrolled in a double-masked, randomized, comparative study and assigned to either indomethacin or diclofenac treatment. Subjective preoperative evaluation of individual susceptibility to pain evoked by topical application of 1% tetracaine vs saline served as reference for further post-operative pain measurement using a visual analog rating scale. Ocular and cephalic pain, itching, foreign body sensation, insomnia, photophobia, blepharospasm as well as systemic analgesic medication and alcohol intake were monitored for 3 days following photoablation as well as the re-epithelialization process. Both solutions significantly reduced pain on the first day following excimer laser PRK, and this activity was maintained until the end of the observation period. At Day 0 the first measure of pain level was slightly higher in the indomethacin group (p < 0.05) and could be related to a possible anaesthetic effect of Diclofenac. During the follow-up the oral intake of analgesics was higher in the diclofenac group, however this difference was not significant. Wound healing rate was not affected by indomethacin or diclofenac administration. These data suggest that both 0.1% indomethacin and 0.1% diclofenac ophthalmic solutions may help to control the pain induced by excimer laser PRK without any deleterious effect on corneal wound healing.