Objectives: MRSA Skin and soft tissue infections represent a major clinical problem in Colombia. The aim of this study was to evaluate risk factors associated with MRSA SSTI in Colombia. Methods: We performed a multicenter cohort study with nested case-control design. Patients with SSTI with at least 48 hours of inpatient care were included. Patients with MRSA SSTI were considered the case group and patients with either non-MRSA SSTI or with MSSA SSTI were the control groups. We used multivariate logistic regression approach to evaluate risk factors associated with MRSA SSTI using two different statistical models. Results: We included 1,134 patients. Cultures were available for 706 patients of which 36.7% (n=259) were Staphylococcus aureus. MRSA was confirmed in 68.3% of the S. aureus cultures. In the first model independent risk factors for MRSA SSTI were presence of abscesses (P<.0001), furunculosis (P= .044), age 18 - 44 years (P= <0.0001), prior outpatient treatment in the preceding index visit (P=.010) and report of an insect bite (P=.027). In the second model the main risk factor found was prior outpatient treatment in the preceding index visit (P= .013). Conclusions: Although clinicians should consider MRSA when designing the initial empirical treatment for purulent SSTI in Colombia.