This study was designed to compare the efficacy of two artificial tears both containing hyaluronic acid but differing in their osmolarity. A multicentric double-masked, crossover clinical trial was performed in which 158 subjects were randomized to receive either hypotonic or isotonic artificial tears up to 6 times a day. Both treatments were effective in improving signs and symptoms to a similar extent. No adverse events were reported. It was concluded that hypotonic and isotonic eye drops are comparable for the symptomatic treatment of patients suffering from dry eye syndrome.