This article analyzes the confirmation and tenure of 2,300 Senate-confirmed, presidential appointees to U.S. government agencies between 1989 and 2009, linking patterns of appointee confirmation and tenure to institutional politics, appointee independence, and agency context. Consistent with prior research, the authors find that nominees of new, powerful, and popular presidents enjoy expedited Senate confirmation. Contentious congressional committee oversight, by contrast, tends to delay confirmation and reduce tenure. Agency heads and positions insulated from removal, such as for fixed-term positions and inspectors general, increase tenure. Extending empirical research, the analysis highlights program- and agency-level variations that speak to the many contingencies shaping appointee politics. Appointee positions associated with national security and broad statutory discretion receive expedited confirmation. Agencies with more professionals are associated with increased tenure, whereas agencies with more appointees among managers see shorter tenures. The results speak to scholarship on appointee politics and to public knowledge about the role of appointments in American government.