This paper examines the influence of Research and Development (R&D) strategy on firm performance controlling for external environment. In this turbulent era, several firms build their competitive advantage on their innovation competence investing on R&D. Drawing upon a sample of 248 firms located in Greece, a structured questionnaire was developed to measure R&D strategy, external environment (dynamism, complexity, munificence, technological) and firm performance (financial, market, innovation, growth and organizational). The importance of R&D strategy in explaining the variance of all performance dimensions is confirmed with innovation performance playing a dominant role. Results indicate that R&D strategy is the most crucial antecedent of firm performance, controlling for business environment. Among environmental dimensions, only dynamism exerts statistical significant relationships. Regarding organizational size, larger firms possess a competitive advantage in the market, enjoying dominant market shares, while smaller firms exhibit supremacy regarding their innovative behavior.