© Copyright 2016 American Academy of Optometry. Purpose. To evaluate contact lens (CL) storage case contamination when used with four different CL care solutions during daily wear of three different CL materials. Methods. A parallel, prospective, bilateral, randomized clinical trial (n = 38) was conducted. Subjects were randomly assigned to use one of three CL materials (etafilcon A, senofilcon A, or galyfilcon A) on a daily wear basis. Subsequently, each subject randomly used one of four different CL care solutions (Biotrue, OPTI-FREE PureMoist, RevitaLens OcuTec, and CLEAR CARE) for 2 weeks, along with their respective storage cases. After every 2-week period, their storage cases were collected and the right and left wells of each storage case were randomized for two procedures: (1) microbial enumeration by swabbing the storage case surface and (2) evaluation of biofilm formation (multipurpose solution cases only) using a crystal violet staining assay. Results. More than 80% of storage cases were contaminated when used in conjunction with the four CL care solutions, irrespective of the CL material worn. Storage cases maintained with CLEAR CARE (mean Log colony forming units (CFU)/ well ± SD, 2.0 ± 1.0) revealed significantly (p < 0.001) greater levels of contamination, compared to those maintained with Biotrue (1.3 ± 0.8) and RevitaLens OcuTec (1.2 ± 0.8). Predominantly, storage cases were contaminated with Gram-positive bacteria (≥ 80%). There were significant differences (p = 0.013) for the levels of Gram-negative bacteria recovered from the storage cases maintained with different CL care solutions. Storage cases maintained withOPTI-FREE PureMoist (0.526 ± 0.629) showed significantly higher biofilm formation (p = 0.028) compared to those maintained with Biotrue (0.263 ± 0.197). Conclusions. Levels of contamination ranged from 0 to 6.4 Log CFU/storage case well, which varied significantly (p < 0.001) between different CL care solutions, and storage case contamination was not modulated by CL materials.