A double-blind randomized clinical study was conducted to determine whether nicardipine hydrochloride was a useful treatment for dry eye.We examined its effect on the tear film, ocular surface and ocular comfort. Nicardipine hydrochloride, 3-isobutyl-1-methylxanthine and pilocarpine hydrochloride were dissolved in an artificial tear vehicle and applied topically to one eye of 12 subjects on separate days. Ocular physiology, ocular comfort and tear volume were assessed. The trial was repeated with nicardipine in an aqueous gel vehicle. Tears were collected and assessed for protein concentration and protein profile, using electrophoresis and mass spectrometry. Nicardipine induced conjunctival redness and symptoms of dryness and irritation. There was no change in total tear protein concentration or volume. An increase in a 68 kDa protein was observed, this was probably due to conjunctival vessel dilation and leakage of albumin. The adverse symptomatology and increased conjunctival redness experienced with nicardipine make it an undesirable treatment for dry eye.