Does familiarity with alliance partners promote breakthrough innovations? This study draws on the literature of interorganizational routines to examine the impact of repeated R&D collaborations within a firm's alliance portfolio on its breakthrough innovations. Specifically, we contend that the benefits and liabilities of interorganizational routines, arising from alliance partner repeatedness at a firm's alliance portfolio level, lead to an inverted U-shaped relationship between alliance partner repeatedness and breakthrough innovations. Further, we build on the recent theoretical development of interorganizational routines to propose that technological dynamism will make the inverted U-shaped relationship steeper. Analyses of approximately 230 firms in the US biopharmaceutical industry from 1983 to 2002 support our hypotheses. Our findings provide important implications for research on alliance portfolio and management of firm innovation.