Objective The objective of this study is to identify barriers for the timely delivery of endovascular thrombectomy (EVT) and to investigate the effects of potential workflow improvements in the acute stroke pathway. Design Hospital data prospectively collected in the MR CLEAN Registry were linked to emergency medical services data for each EVT patient and used to build two Monte Carlo simulation models. The ‘mothership (MS) model’, reflecting patients who arrived directly at the comprehensive stroke centre (CSC); and the ‘drip and ship’ (DS) model, reflecting patients who were transferred to the CSC from primary stroke centres (PSCs). Setting Northern region of the Netherlands. One CSC provides EVT, and its catchment area includes eight PSCs. Participants 248 patients who were treated with EVT between July 2014 and November 2017. Outcome measures The main outcome measures were total delay from stroke onset until groin puncture, functional independence at 90 days (modified Rankin Scale 0–2) and mortality. Results Barriers identified included fast-track emergency department routing, prealert for transfer to the CSC, reduced handover time between PSC and ambulance, direct transfer from CSC arrival to angiography suite entry, and reducing time to groin puncture. Taken together, all workflow improvements could potentially reduce the time from onset to groin puncture by 59 min for the MS model and 61 min for the DS model. These improvements could thus result in more patients—3.7% MS and 7.4% DS—regaining functional independence after 90 days, in addition to decreasing mortality by 3.0% and 5.0%, respectively. Conclusions In our region, the proposed workflow improvements might reduce time to treatment by about 1 hour and increase the number of patients regaining functional independence by 6%. Simulation modelling is useful for assessing the potential effects of interventions aimed at reducing time from onset to EVT.