This article describes how long-term collaborators interpret substantive differences of opinion and the strategies they use to negotiate them. Long-term collaborators are coauthors who have had a working relationship for ten or more years. Differences of opinion refer to differences in interpretation about substantive issues related to research and writing, not to other kinds of differences such as in personality or working style or disagreements about organizational or administrative issues. An exploration of how collaborators deal with differences of opinion can add to our understanding about how to enhance the effectiveness and sustainability of research collaborations and to identify circumstances where collaboration contributes to innovation or significant new insight to scientific knowledge. It also adds to the understanding about ways to create a collaborative culture that embraces difference. Findings from this research support the contribution of social and relational dynamics to knowledge production and add to the literature about collaborative learning by suggesting that it is not just the dynamics of the collaborative process that can promote innovation, but also the relational dynamics.