We’re thrilled to present our first journal club episode, focusing on tenecteplase for ischaemic stroke in the 4.5-24 hour time window in patients with large vessel occlusions (LVOs) in whom mechanical thrombectomy is not an available option (the TRACE-III study, published in the New England Journal of Medicine; NEJM in 2024). This is a landmark study extending the thrombolysis timing window beyond 9 hours for the first time, although with a number of caveats as discussed in the episode. This episode, in addition to teaching you about the evolving landscape of hyperacute therapy options in stroke, teaches you how to critically evaluate a medical journal article, and how to then apply the journal article to your clinical practice, and determine in what ways (if any) that the article is practice changing. This is a more advanced episode, better suited to neurology trainees and neurologists, although more junior audience members will also find it valuable through its global significance in extending the thrombolysis window in places where mechanical thrombectomy is not available, and through its providing a step-by-step worked example in regard to how to critically evaluate a neurology article, an essential and highly transferable skill across clinical medicine as a whole.Correction: At various times when discussing the results section, I refer to the ‘placebo group’ (as a force of habit, apologies!) as opposed to correctly saying the ‘control group’ in this case, given that this was an open-label study at the time of randomisation (not placebo-controlled) and then later blinded at the time of outcome measurement and statistical analysis, as was discussed in the episode.