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Prior research argues that alignment between business and information systems (IS) strategies enhances organizational performance. However, factors affecting alignment have received relatively little empirical attention. Moreover, IS strategic alignment is assumed to facilitate the performance of all organizations, regardless of type or business strategy. By using two studies of business firms and academic institutions, this paper: 1) develops and tests a model relating alignment, its antecedents, and its consequences and 2) examines differences in these relationships across organizational types and strategies. Findings indicate that alignment depends on shared domain knowledge and prior IS success, and also support the expected positive impact of alignment on organizational performance. Differences across Prospector, Analyzer, and Defender business strategies are examined. A key research contribution is …