Abstract: This study aims to show the impact of applying six sigma methodologies on performance of pharmaceutical firms in Jordan. For the purpose of gathering, the data a well-structured questionnaire has been developed, the population includes all workers and service recipients of pharmaceutical firms while the sample considered those who are directly dealt with or related to the total quality management which consisted of senior management and departments related to the overall quality, unit managers and heads of departments. A correlational descriptive analytical method was used for data analysis and hypotheses testing. A number of statistical tools and methods were used such as the arithmetic mean, standard deviation and canonical analysis. The results reached showed the existence of the effect which is statistically significant at the level of significance (0.05 α≤ standards for six sigma; continuous improvement, customer focus, prevention, commitment and support of senior management) on performance. Therefor, it has been conclude that the effect six sigma on the firm’s performance is an important topic and needs to be studied deeper, especially in the present time, due to its impact on the reality and the future of the surveyed firms. The study recommends that its highly needed to always gain the support of senior management to adopt six sigma style and improved service that satisfies customer’s needs and desires.