Enterprise information systems, such as Enterprise Resource Planning (ERP) system, have been applied to integrate business processes within a global manufacturing enterprise. Recently, the inter-organizational systems are applied to assist in business data sharing and collaboration among enterprises based on the ERP application. However, their resource requirements and failure rates are high so that many enterprises are concerned about the Business-to-Business (B2B) effectiveness. In this research, we study global manufacturing enterprises which developed their B2B systems with Taiwanese government sponsorship successfully. The B2B effectiveness is evaluated by the indexes of operational efficiency and profitability, while the business scale, Electronic Data Interchange (EDI) induced supplier numbers, and application scope are considered to be influencing factors. After the evidence of multiple regression models testing, the results show that only the application scope has a significant impact on the profitability. We discuss these results from the perspective of enterprise integration as well as the system application scope and give suggestions to global manufacturing enterprises which want to apply inter-organizational systems.