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Background: Acute stroke treatment in mobile stroke units (MSU) is feasible and reduces time‐to‐treatment, but the optimal staffing model is unknown. We wanted to explore if integrating thrombolysis of acute ischemic stroke (AIS) in an anesthesiologist‐based emergency medical services (EMS) reduces time‐to‐treatment and is safe. Methods: A nonrandomized, prospective, controlled intervention study. Inclusion criteria: age ≥18 years, nonpregnant, stroke symptoms with onset ≤4 h. The MSU staffing is inspired by the Norwegian Helicopter Emergency Medical Services crew with an anesthesiologist, a paramedic‐nurse and a paramedic. Controls were included by conventional ambulances in the same catchment area. Primary outcome was onset‐to‐treatment time. Secondary outcomes were alarm‐to‐treatment time, thrombolytic rate and functional outcome. Safety outcomes were symptomatic intracranial hemorrhage and mortality. Results: We included 440 patients. MSU median (IQR) onset‐to‐treatment time was 101 (71–155) minutes versus 118 (90–176) minutes in controls, p = 0.007. MSU median (IQR) alarm‐to‐treatment time was 53 (44–65) minutes versus 74 (63–95) minutes in controls, p < 0.001. Golden hour treatment was achieved in 15.2% of the MSU patients versus 3.7% in the controls, p = 0.005. The thrombolytic rate was higher in the MSU (81% vs 59%, p = 0.001). MSU patients were more often discharged home (adjusted OR [95% CI]: 2.36 [1.11–5.03]). There were no other significant differences in outcomes. Conclusions: Integrating thrombolysis of AIS in the anesthesiologist‐based EMS reduces time‐to‐treatment without negatively affecting outcomes. An MSU based on the EMS enables prehospital assessment of acute stroke in addition to other medical and traumatic emergencies and may facilitate future implementation. [ABSTRACT FROM AUTHOR]