Purpose Biodegradable temporizing matrix (BTM) is a dermal regeneration template with a widening array of applications, including treatment of major burns, necrotising fasciitis, reconstruction of free flap donor sites and cutaneous malignancies. Currently, use of BTM requires split-thickness skin grafting (STSG) 4-6 weeks after its application. This is associated with cost and further surgical morbidity. Use of BTM is therefore restricted for patients who are poor surgical candidates or who may require multiple applications. There have been some reports of wounds treated with BTM being left to reepithelialise by secondary intention, without a STSG. We demonstrate the largest case series to date on BTM use with reepithelialisation by secondary intention. Methods We present a retrospective review of patients treated by the surgical oncology team at Westmead Hospital. BTM was applied to the wound bed and left to integrate before delamination at 4-6 weeks. Following delamination, wounds were left to re-epithelialise by secondary intention. Results Thirteen patients with an average age of 81.31 years (range 68–92) were included. A total of 25 defects were treated, with an average lesion size of 13.72 cm² (range 3–100 cm²). The average time to confirmed healing was 140 days (range 61 to 248). Conclusion The application of BTM with re-epithelialisation by secondary intention was shown to be a safe and efficacious method of hybrid wound healing for managing defects following skin cancer resection or flap donor site closure. This method is particularly useful for patients with extensive skin cancer history and those at high risk of surgical morbidity.