Research has identified numerous factors that influence suspects during police interrogations. However, the dynamics between individuals’ physiologic reactivity and their confession decision making is in its infancy. This research sought to advance the interrogation literature by examining the relationships among different interrogation tactics, suspects’ resistance to confess, and their physiologic reactivity during a mock interrogation. After manipulating innocence and guilt, participants (N = 154) were accused and interrogated using either a minimization or false evidence tactic. Participants’ physiologic reactivity was operationalized using their systolic blood pressure, and confession resistance was quantified as the number of times participants refused to confess. Results demonstrated that participants exhibited more physiologic reactivity after being confronted with false evidence ploys than minimization. Furthermore, innocent participants resisted confessing more than guilty participants, but innocents confronted with false evidence resisted confessing to a greater extent than innocents confronted with minimization. Moreover, a moderated-mediation analysis indicated that although innocents resisted confessing more when confronted with false evidence than those confronted with minimization, these innocents sustained a significantly higher level of physiologic reactivity. The results of the conditional indirect relationship suggest that innocents who are confronted with false evidence may resist the most but at a cost—their greater resistance may exhaust them and undermine subsequent decision making. These results offer support for reforms aimed at reducing the length of interrogations and the use of interrogation tactics that unnecessarily increase false confession rates. (PsycINFO Database Record (c) 2018 APA, all rights reserved)