The optimal prehospital blood pressure in patients following traumatic brain injury (TBI) remains controversial. We aimed to assess the association between the systolic blood pressure (SBP) at emergency department triage and patient outcomes following isolated moderate-to-severe TBI. We conducted a cross-national multicenter retrospective cohort study using the Pan-Asia Trauma Outcomes Study database from January 1, 2016, to November 30, 2018. The enrollees were adult patients with isolated moderate-to-severe TBI defined by the International Classification of Diseases code, a Glasgow Coma Scale (GCS) <13 at triage, and a nonhead Abbreviated Injury Scale ≤3. The studied variables were SBPs at triage categorized into different ranges. The primary outcome was 30-day mortality, and the secondary outcome was poor functional status at hospital discharge defined by the modified Rankin Scale ≥4. Multivariable logistic regression was applied to adjust for confounders including country, sex, age, mechanism of injury, prehospital vascular access, respiratory rate, GCS, oxygen saturation, intubation, Injury Severity Score, head surgery, intensive care unit admission, and length of hospital stay. Subgroup analyses were performed on different severity of TBI. A total of 785 patients (median age, 42 years; male patients 77.5%; mean SBP at triage, 136.3 ± 33.1 mmHg) were included in the primary analysis. The lowest 30-day mortality rate existed in patients with SBP of 100-119 mmHg. Taking it as baseline, the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of SBP <100 mmHg, 120-139 mmHg, 140-159 mmHg, and ≥160 mmHg were 7.05 (2.51-19.78), 3.14 (1.14-8.65), 2.91 (1.04-8.17), and 3.28 (1.14-9.42). As for the secondary outcome, the aORs and 95% CIs were 1.36 (0.68-2.68) of <100 mmHg, 0.99 (0.57-1.70) of 120-139 mmHg, 1.23 (0.67-2.25) of 140-159 mmHg, and 1.52 (0.78-2.95) of ≥160 mmHg. Subgroup analyses revealed trends of the best outcomes in both moderate and severe TBI patients with SBP 100-119 mmHg, whereas statistical significance appeared only in patients with severe TBI. SBP of 110-119 mmHg at triage is associated with the lowest 30-day mortality in patients following isolated moderate-to-severe TBI and possibly related to a better functional outcome.