Background To investigate response of dissolving collagen contact lenses as an alternative for bandage contact lenses, for the post-interventional care of epithelial defects after corneal cross-linking (CXL) treatment for keratoconus. Patients and methods Follow-up visits were performed at day 1, 4 and 1 month after the intervention. We reviewed notes for re-epithelialization, comfort/pain and any untoward effects of Collagen SOFT SHIELD (R). Assessment included visual acuity (VA), refraction (SE); corneal haze, epithelial erosion and pain status were assessed subjectively on a 4-point scale, from 0 (none) to 3 (severe). Results Thirty consecutive CXL patients with collagen shield application after CXL were included. Mean age was 28 years (range from 16 to 51 years old). Pre-CXL VA was 0.7 logMAR IQR 0.4-1.0; post-CXL VA at day 4 and month 1 was 0.6 logMAR IQR 0.4-0.9. Post-operative mean SE was 5.5D +/- 4.1D. In all patients, the Collagen SOFT SHIELD (R) was completely dissolved at the 4-day follow-up visit. In most cases, epithelial defect was closed at day 4, on average 0.8 +/- 0.5 days post-intervention; all epithelial defects were closed by month 1. Haze was minimal (mean haze score 1.4 +/- 0.7 at day 4 and 1.0 +/- 0.6 at 1 month). No adverse effects such as infection were observed. Conclusions This study indicates that Oasis Collagen SOFT SHIELD (R) is valuable and safe alternative to standard bandage contact lens for the treatment of epithelial defects. This outcome may be of particular interest in patients where the contact lens removal is likely to be problematic.