<p>A core clinical feature of posttraumatic stress disorder (PTSD) is recurrent reexperiencing of the traumatic event in the form of intrusive memories. Doxycycline is a matrix metalloproteinase 9 (MMP-9) inhibitor. MMP-9 is required for late-phase, NMDA receptor-dependent long-term potentiation in the hippocampus and the basal and central amygdala nuclei, which are important to various forms of learning and memory. Here we examined the effect of doxycycline on the development of intrusive memories in a pre-registered randomized, double-blind, placebo-controlled trial (<a href="https://osf.io/72ys9">https://osf.io/72ys9</a>). Healthy females (N = 80) received 200 mg doxycycline or placebo 4.5 h before exposure to film footage depicting strong interpersonal violence. Participants then completed an intrusion diary for one week. Most participants, 92%, experienced intrusive memories following the trauma film. There was no evidence that doxycycline and placebo groups differed in frequency, distress, and vividness of daily intrusive memories models. The doxycycline group showed enhanced arousal, indexed by skin conductance when exposed to reminder cues, and better performance in a memory task about film content compared to placebo one-week post-film. Based on our findings, the MMP9-inhibitor doxycycline did not impair the development of intrusive memories and was associated with increased arousal and improved retrieval of experimental trauma memory one week later.</p>