The authors evaluated the efficacy of all-trans retinoic acid (vitamin A) ointment as a treatment for keratoconjunctivitis sicca (KCS) in a group of 11 patients selected on the basis of clinical history, slit-lamp examination results, rose Bengal staining, and tear film osmolarity. In this open-label crossover study, vitamin A ointment was no more effective than placebo in increasing tear secretion, as indicated by Schirmer test with proparacaine or tear film osmolarity, or in decreasing ocular surface disease, as indicated by rose Bengal staining. Seven patients stated some preference for the placebo ointment, two patients for the vitamin A ointment, and two patients had no preference.