Objectives To investigate differences in antibiotic prescription for patients with hard-to-heal ulcers assessed using a digital decision support system (DDSS) compared with those assessed without using a DDSS. A further aim was to examine predictors for antibiotic prescription. Design Register-based study. Setting In 2018-2019, healthcare staff in primary, community and specialist care in Sweden tested a DDSS that offers a mobile application for data and photograph transfer to a platform for multidisciplinary consultation and automatic transmission of data to the Registry of Ulcer Treatment (RUT). Register-based data from patients assessed and diagnosed using the DDSS combined with the RUT was compared with register-based data from patients whose assessments were merely registered in the RUT. Participants A total of 117 patients assessed using the DDSS combined with the RUT (the study group) were compared with 1784 patients whose assessments were registered in the RUT without using the DDSS (the control group). Primary and secondary outcome measures The differences in antibiotic prescription were analysed using the Pearson's chi(2) test. A logistic regression analysis was used to check for influencing factors on antibiotic prescription. Results Patients assessed using a DDSS in combination with the RUT had significantly lower antibiotic prescription than patients entered in the RUT without using the DDSS (8% vs 26%) (p=0.002) (only healed ulcers included). Predictors for antibiotic prescription were diabetes; long healing time; having an arterial, neuropathic or malignant ulcer. Conclusions A DDSS with data and photograph transfer that enables multidisciplinary communication appears to be a suitable tool to reduce antibiotic prescription for patients with hard-to-heal ulcers.