This study considers how cross-sectional differences and intertemporal variations in interdependencies between productive activities at the industry level moderate the contribution of exploration to long-run organizational performance. We use patent data to measure interdependencies between productive activities at the industry level and computer-assisted content analysis to derive firms’ orientation toward exploration. We also introduce statistical techniques to control bias in estimates induced by potential sources of endogeneity. Our analysis shows that exploration largely contributes positively to long-run organizational performance. This positive effect is stronger in industries with more extensive levels of interdependency or that exhibit more changes in such interdependencies. This study shows the unique and contingent ways in which exploration affects long-run performance. We hope our ideas will influence several areas of future research, not the least of which involves exploration and interdependencies in developing our understanding of organizational success.