Bacterial proliferation plays a well-known role in delayed tissue healing. To date, the presence of microorganisms on the wound bed can be detected by skin swabs or skin biopsies. A novel noninvasive fluorescence imaging device has recently allowed real-time detection of bacteria in different types of wounds through endogenous autofluorescence. The fluorescence signals detected by the device provide health workers with a visual indication of the presence, load, and distribution of bacteria. The aim of our study was to evaluate the level of bacterial colonization in perilesional skin of patients affected by venous leg ulcers treated with 2 different types of bandages: short stretch bandage and zinc oxide bandage. We conducted a monocentric prospective study, enrolling 30 patients with venous leg ulcers, divided into 2 groups: group A was treated with short stretch bandage and group B with zinc oxide bandage. A complete patient's assessment was performed once a week for 3 weeks. Levels of potentially harmful bacteria in perilesional skin were detected using a fluorescent device by 2 experienced operators on the frames taken at individual injuries, while pain was evaluated with the Numerical Rating Scale. After 3 weeks, we observed a reduction in the bacterial colonization levels of the perilesional skin by 68.67% for group A and 85.54% for group B. All the patients had a statistically significant reduction in bacterial load ( P < .001), and a statistically significant difference was identified between the 2 groups ( P = .043). No statistically significant differences were found between the 2 groups in terms of pain relief ( P = .114). Our study demonstrated that the application of zinc oxide bandage provides a higher reduction in bacterial load perilesional skin. On the other hand, we found no difference between the 2 bandages in terms of pain symptom reduction