SIGNIFICANCE There remains only a small amount of data from human studies demonstrating the effect of contact lens/lens care solution combinations on the deposition of lipids. Therefore, information on the degree to which modern materials deposit lipids when used with contemporary care solutions would be valuable. PURPOSE The present study aims to determine the effect of lens care system combinations on levels of total lipid, cholesterol, and cholesteryl esters extracted from three different contact lenses (CLs) when used with four contemporary care systems. METHODS Experienced CL wearers were recruited to participate in this study. Combinations of three CLs (etafilcon A [ETA], galyfilcon A [GALY], and senofilcon A [SENO]) and four CL care solutions (Biotrue, ClearCare, OPTI-FREE PureMoist, and RevitaLens Ocutec) were investigated. A total of 791 CLs were analyzed. Subjects were randomized to one lens type and then used all four lens care solutions in random sequence for 10-14 days before the CLs were collected and analyzed for the amount of cholesterol, cholesteryl esters, and total lipids. RESULTS The mean range of cholesterol recovered across the different care solutions was 0.34-2.77 μg/lens, 3.48-4.29 μg/lens, and 4.75-6.20 μg/lens for ETA, SENO, and GALY lenses, respectively. Use of OPTI-FREE PureMoist with ETA lenses led to a significantly greater amount of cholesterol being recovered when compared to the use of the other solutions with ETA lenses (P <.05). The mean range of cholesteryl esters recovered across different care solutions was 1.31-2.02 μg/lens, 6.43-7.19 μg/lens, and 7.96-10.13 μg/lens for ETA, SENO, and GALY lenses, respectively. There were no differences in the amount of cholesteryl esters and total lipids extracted for a given lens type when used with any of the four care solutions (P >.05). CONCLUSIONS This study did not demonstrate conclusively that any of the solution/CL combinations were superior to any of the other combinations when the amounts of lipid deposition were compared among the tested lenses.