The use of dermal substitutes is considered an effective treatment in several pathologies involving skin damage, mainly extensive burns and trauma. Treatment alternatives entail performing flaps or autografts. The purpose of this cross-sectional study is to assess the clinical effects and cost-effectiveness of dermal substitutes in surgical procedure in complex wound healings of adult trauma patients. The study includes 52 patients who received dermal substitutes (n = 25) between 2007 and 2012 and patients treated between 2006 and 2011 who received standard treatment (n = 27). All patients presented with posttraumatic soft tissue defects with bone and/or tendon exposure. Differences in costs, mean differences in Euros and Euros per square centimeter, and clinical data were collected as outcome measures. Pearson’s correlations were used to assess the relationship between total costs with sociodemographic data and clinical services to different healthcare providers (clinical data and costs were recorded for both groups). No relevant differences on acceptance rates were noticed amongst groups. Surgery costs were shown to be significantly reduced in the dermal substitutes group (P < 0.01) even though total costs (surgery + hospitalization) did not exhibit a significant difference. Surgical time was significantly reduced in the dermal substitutes group (1.81 min/cm2 lesions) as compared with the standard group (6.08 min/cm2 lesions). The current study suggests that not only clinical but also possible economic and logistical advantages in choosing dermal substitutes may exist.