©Tiago K Colicchio, James J Cimino, Guilherme Del Fiol. The US health system has recently achieved widespread adoption of electronic health record (EHR) systems, primarily driven by financial incentives provided by the Meaningful Use (MU) program. Although successful in promoting EHR adoption and use, the program, and other contributing factors, also produced important unintended consequences (UCs) with far-reaching implications for the US health system. Based on our own experiences from large health information technology (HIT) adoption projects and a collection of key studies in HIT evaluation, we discuss the most prominent UCs of MU: failed expectations, EHR market saturation, innovation vacuum, physician burnout, and data obfuscation. We identify challenges resulting from these UCs and provide recommendations for future research to empower the broader medical and informatics communities to realize the full potential of a now digitized health system. We believe that fixing these unanticipated effects will demand efforts from diverse players such as health care providers, administrators, HIT vendors, policy makers, informatics researchers, funding agencies, and outside developers; promotion of new business models; collaboration between academic medical centers and informatics research departments; and improved methods for evaluations of HIT.