This paper asks whether legislators are able to benefit from opposing their party on one or more high-profile issues. Such a strategy likely entails a tradeoff, as it might on the one hand attract cross-over support from opposite-party voters but, on the other hand, alienate co-partisan voters who make up the legislator’s “primary constituency.” Using data from a 2006 national survey in which citizens are asked their own positions on seven high-profile issues voted on by the U.S. Senate, as well as how they believe their state’s two senators to have voted on these issues, I find that senators generally do not benefit from voting against their party. First, same-party voters who oppose a senator’s party-deviating stance are more likely to notice this behavior than are opposite-party voters who should be pleased by a legislator’s vote against her party. Second, the uptick in electoral support that senators receive from the small subset of opposite-party voters who do notice their deviation on a particular issue is substantively small, while the decrease in their job approval among their co-partisan constituents–the voters upon whom senators must rely to win re-nomination–is non-trivial. These findings have important implications for legislators’ strategic incentives and offer hints as to why the last decade has seen a substantial number of re-election losses by moderate senators representing states in which their party is not favored, as well as a non-trivial number of serious primary challenges–some of which have succeeded–to senators who compile moderate voting records.