We aimed to determine the incidence of bacteremia and prognostic effects of prompt administration of appropriate antimicrobial therapy (AAT) on nontraumatic out-of-hospital cardiac arrest (OHCA) patients achieving a sustained return of spontaneous circulation (sROSC), compared with non-OHCA patients. In the multicenter case-control study, nontraumatic OHCA adults with bacteremia episodes after achieving sROSC were defined as case patients, and non-OHCA patients with community-onset bacteremia in the emergency department were regarded as control patients. Initially, case patients had a higher bacteremia incidence than non-OHCA visits (231/2171, 10.6% vs. 10,430/314,620, 3.3%; p < 0.001). Compared with the matched control (2288) patients, case (231) patients experienced more bacteremic episodes due to low respiratory tract infections, fewer urosepsis events, fewer Escherichia coli bacteremia, and more streptococcal and anaerobes bacteremia. Antimicrobial-resistant organisms, such as methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing Enterobacteriaceae, were frequently evident in case patients. Notably, each hour delay in AAT administration was associated with an average increase of 10.6% in crude 30-day mortality rates in case patients, 0.7% in critically ill control patients, and 0.3% in less critically ill control patients. Conclusively, the incidence and characteristics of bacteremia differed between the nontraumatic OHCA and non-OHCA patients. The incorporation of blood culture samplings and rapid AAT administration as first-aids is essential for nontraumatic OHCA patients after achieving sROSC.