Pharmaceutical companies play a significant role in ensuring that people have access to high-quality and affordable medical services. They provide a wide range of medical services, from preventative care to emergency services. Despite the contribution of pharmaceutical companies to the social and economic growth of citizens in both developed and developing countries, their performance may not have been as expected. This is evident in the poor level of competitive advantage, decline in market share growth, dwindling financial growth, decline in productivity and customer retention. This study investigated the effect of entrepreneurial orientation on competitive advantage of quoted pharmaceutical companies in Nigeria. The study adopted a survey research design. The population of the study was 308 executive manager, directors and marketing department official in these quoted pharmaceutical companies in Nigeria. Data was collected using a valid and reliable questionnaire with a Cronbach alpha value greater than 0.7. Data were analysed using both descriptive and inferential tools. Multiple and Hierarchical Regression Analysis were used to determine the effect of the variables using Statistical Package for Social Science (SPSS). The results revealed that entrepreneurial orientation had significant effect on competitive advantage of quoted pharmaceutical companies in Nigeria (Adj. R2 = 0.265; F (5, 296) = 22.726, p < 0.05). The study expanded the frontier of knowledge on Nigerian pharmaceutical industry performance by unbundling entrepreneurial orientation to see how each element affected competitive advantage. The study is an original study and it adds to scholarly debate on entrepreneurial orientation and competitive advantage of quoted pharmaceutical companies as the adoption of managers’ perspectives was subjective, and competitive advantage is not static, hence secondary data could be a future option for scholars. Keywords: Entrepreneurial orientation, Competitive advantage, Competitive Aggressiveness, Entrepreneurial autonomy, Innovation.