This study determined whether comprehensive microbiological analysis offered real predictive value in terms of healing outcome, and assessed the clinical usefulness of surface swabs vs. tissue biopsies for clinically noninfected leg wounds. The wound microflora of 70 patients with chronic venous leg ulcers was quantified after sampling by swabbing and biopsy. A highly significant association between wound surface area at 4 weeks and eventual healing at 6 months was found (p<0.001), although initial wound size, sex, height, and weight were not significant predictors of outcome (p>0.1). A significant association between healing and bacterial diversity in the wound as assessed by swab (p=0.023) was demonstrated. Furthermore, the bacterial density of wound surface area by swab (CFU/mL; p=0.018) or biopsy (CFU/g tissue; p=0.038) were shown to be independent predictors of nonhealing. Logistic regression showed that microbiological analysis of biopsies provided no additional prognostic information when compared with analysis of the surface microflora (p=0.27). Hence, if biopsies do not contribute significantly to patient management, their use should be discouraged in clinically noninfected wounds. Furthermore, independent predictors of healing, such as wound surface microbial diversity and density, could identify patients likely to have an unfavorable outcome and to whom resources should be targeted.