Open innovation is a young arena in research that is fascinating the attention of a growing number of scholars. However, there are not enough studies that investigate open innovation performance. The pharmaceutical industry with the most Research and Development (R&D) intensity has been targeted by this new paradigm. This study explores the effect of entrepreneurial orientation on open innovation performance, considering the mediating role of desorptive capacity, which is defined as the firms capability to recognize outward technology transfer opportunities and to facilitate it. We use structural equation modeling to examine the hypotheses on a dataset from 100 Iranian pharmaceutical manufacturers in 2018. The results of the study support our conceptual model. Our findings indicate that a firms entrepreneurial orientation and desorptive capacity have a positive effect on its open innovation performance. Moreover, desorptive capacity has a mediating effect in the relation of entrepreneurial orientation and open innovation performance. This denotes that our new model contributes to the concept of desorptive capacity in the context of open innovation.