Objective  To evaluate the clinical effect and safety of esculin and digitalisglycosides eye drops in patients with asthenopia after laser in situ keratomileusis (LASIK) surgery. Methods  This was an open， multicenter， random and antithetical prospective clinical trial. Post-LASIK surgery patients were chosen from seven hospitals across China from July 2008 to January 2009. Some patients received esculin and digitalisglycosides eye drops and others served as controls. Symptoms of asthenopia， uncorrected visual acuity (UCVA)， refraction， amplitude of accommodation， lag of accommodation， accommodative sensitivity and positive/negative relative accommodation were compared between the two groups at different time points. A total of 195 patients (88 males and 107 females) were included in the study with a mean age of (25.4±5.9)years. Among the 195 patients， 109 were in the treatment group and 86 were in the control group. Data were analyzed using a nested ANOVA. Results  Blurred vision after reading (F=4.099， P<0.05) and headache or sickness following near work (F=4.344， P<0.05) improved in the treatment group compared to the control group. Accommodative sensitivity (left eye： F=5.895， P<0.05； right eye： F=7.440， P<0.05； both eyes： F=5.323， P<0.05) and negative relative accommodation (F=5.561， P<0.05) were also better in the treatment group. Conclusion  Esculin and digitalisglycosides eye drops can significantly alleviate the symptoms of asthenopia in patients following LASIK surgery. It can also improve the accommodative sensitivity and negative relative accommodation in post-LASIK surgery patients.