Purpose: To compare and evaluate maxillary sinus perforation repair, bone regeneration, and membrane degradation with cross-linked and non-cross-linked collagen membranes in rat sinuses at 2, 4, and 10 weeks, respectively. Materials and Methods: Fifty-one Sprague-Dawley rat models were included in the study. Bilateral maxillary sinus perforations were made with a straight bur. In the control site, cross-linked collagen membrane (Ossix Plus) was placed, and in the test site, non-cross-linked collagen membrane was used (Pro-Tiss). Euthanasia was carried out under carbon dioxide asphyxia where 17 rats were sacrificed at weeks 2, 4, and 10. Histologic evaluation of the specimens was subsequently done. Results: At 2 (P = .001), 4 (P = .031), and 10 (P = .024) weeks, there was a significant regeneration of maxillary sinus lining in sites treated with non-cross-linked collagen membrane over the cross-linked collagen membrane. No significant differences were observed in measures of bone regeneration (P = .92; 10 weeks) and membrane degradation (P = .06; 4 weeks) at the end of the study period between the two groups. Conclusion: The non-cross-linked collagen membrane appears to be more beneficial in maxillary sinus repair. However, it does not seem to confer additional benefits in bone regeneration or membrane degradation over cross-linked collagen membranes. Keywords: cross-linked collagen, guided tissue regeneration, maxillary sinus, non-cross-linked collagen, soft tissue injuries