PURPOSE. To evaluate the dynamic changes of optical quality in patients with dry eye disease (DED) by using a double-pass system. METHODS. Fifty-six patients with DED and 35 control subjects were included in this study. Each patient underwent an evaluation of the ocular surface, using the Ocular Surface Disease Index, tear film breakup time (TBUT), corneal and conjunctival staining (Oxford scale), and Schirmer I test. Using the tear film analysis program of the Optical Quality Analysis System, we recorded the objective scatter index (OSI) every 0.5 seconds within a 20-second period with the subjects asked to blink freely. Several parameters were established to evaluate the dynamic alterations of optical quality and the effects of blinks: OSI standard deviation (SD), Delta OSI, Delta OSI/time, blinking change (BC), blinking frequency (BF), and tolerant limitation (TL). RESULTS. Patients with DED had significant alterations of optical quality compared to control subjects. The Delta OSI, Delta OSI/time, BC, and BF were significantly higher and TL was significantly lower in DED patients than controls. Furthermore, the Delta OSI and Delta OSI/time were also significantly higher in patients with severe DED than patients with mild disease. In univariate analysis, both TBUT and corneal staining were correlated with Delta OSI, Delta OSI/time, and BC. In multivariate analysis, Delta OSI/time was correlated to the corneal staining score. CONCLUSIONS. The double-pass system allowed the monitoring of the dynamic changes of optical quality in patients with DED. Optical quality should be evaluated in patients with DED because these alterations cannot be determined from the classical DED clinical tests.