AIMS: Emergency medical service (EMS) may detect seizure-like activity in addition to agonal breathing in out-of-hospital cardiac arrest (OHCA). This study investigates the incidence and predictors of seizure-like activity in nontraumatic, EMS-witnessed OHCA and their association with clinical outcomes. METHODS: This prospective study explored EMS-recorded concomitant signs/symptoms that lead to the requirement of advanced life support in patients with nontraumatic, EMS-witnessed OHCA. Seizure-like activity includes abnormal/tonic movements and eyeball deviation. Sudden OHCA was defined by the absence of signs/symptoms of impending cardiac arrest at EMS contact or progressive circulatory/respiratory depressions after the EMS contact. Neurologically favorable outcomes were defined as the cerebral performance category score of 1 or 2 at discharge. RESULTS: From April 2012 to March 2020, 465 patients were studied. The incidence of seizure-like activity at cardiac arrest onset was 12.7% (59/465) in all patients with nontraumatic, EMS-witnessed OHCA. Seizure-like activity was common during shockable initial rhythm; in patients with "sudden" OHCA; and in patients who were younger, male, or had a presumed cardiac etiology. In a boosting tree, shockable initial rhythm, "sudden" OHCA, and presumed cardiac etiology were major factors that predicted the incidence of seizure-like activity. Multivariate logistic regression models including and excluding OHCA characteristics revealed that both seizure-like activity and agonal breathing recorded during EMS-witnessed OHCA were associated with favorable outcomes. CONCLUSIONS: Seizure-like activity is a major sign/symptom of the onset of "sudden" cardiac arrest of presumed cardiac etiology, particularly in patients with shockable initial rhythms. Such activity were significantly associated with neurologically favorable outcomes.