The paper analyzes how the traditional variables that define a firm’s organizational structure (formalization, complexity, and centralization) influence knowledge performance (the degree to which a firm generates knowledge and uses it to reach a competitive advantage). Three hypotheses are tested using a sample of 164 large Spanish firms. The results show that organizational complexity and centralization exert a positive and a negative influence, respectively, on knowledge performance, which confirms the two hypotheses related to these variables. However, the analysis reveals no empirical evidence to confirm the hypothesis that formalization and knowledge performance are related positively.