Background: Soft tissue lesions represent a health problem of great magnitude around the world. Multiple drugs have been used in their treatment. Silver sulfadiazine (SSD) and silver nanocrystals (SNC) are among the most used. The purpose of this research was to compare the effectiveness of SSD and SNC regarding the wound granulation rate, treatment time, antibiotic effect, and treatment cost and to determine the frequency of these lesions in participants of this research. Methods: Data were collected from 50 patients with soft tissue lesions in the Regional University Hospital José María Cabral y Báez (HRUJMCB), in Santiago, Dominican Republic. This study was approved by the bioethics committee of the Pontifical Catholic University Madre and Maestra (PUCMM) and the HRUJMCB. Patients were followed up from August 2015 to February 2016. SPSS Statistics program was used to calculate Chi square and assess statistical significance. Results: Fifty patients were included in this study, of whom 56% had diabetic foot ulcers, 22% had vascular ulcers, and 22% had pressure ulcers. In total, 42% of the patients were treated with SSD and 58% with SNC. Granulation rate was 71.4% for SSD and 89.6% for SNC, and positive antibiotic effect was 15.9% for SSD and 25.9% for SNC. A total of 14.4% of patients treated with SSD ended their participation in the research between 8 and 14 days, 37.9% in 15-21 days, and 42.8% in ≥21 days. For SNC, 3.4% of patients concluded their participation in 0-7 days, 34.4% in 8-14 days, 37.9% in 15-21 days, and 24.1% in ≥21 days. The distribution of economic costs in the SSD group was as follows: 42.9%, 57.2%, while in the SNC group, the distribution was as follows: 48.2%; 48.3%;3.4%. Conclusion: There is no statistical significance in the results of this study; however, in percentage, SNC are superior regarding the rate of wound granulation, antibiotic effect, and healing time. Economic cost for both is similar.