Objective: This study aims to describe the crash characteristics, injury outcomes, and risk factors associated with injury severity for motorcycle crashes resulting in hospitalization in Ho Chi Minh City (HCMC), Vietnam.Methods: A cross-sectional study was undertaken of motorcyclists who were injured as the result of a crash and were admitted to hospital for more than 24 h. Information was collected using a researcher-administered questionnaire and a medical record review. Descriptive statistics and a multiple logistic regression model were undertaken. The outcome of interest was severity of the injury, measured using the Injury Severity Score (ISS).Results: A total of 352 hospitalized motorcyclists were included in the study, of which 6.8% (n = 24) were classified as severe injuries (ISS > 15). At the time of the crash, 41% of participants were not licensed to drive a motorcycle, 26% were speeding, 13% were not wearing a helmet, and 9% were using their mobile phone. The results of the multiple logistic regression model found that not being licensed to drive a motorcycle (adjusted odds ratio [AOR] = 3.32; 95% confidence interval [CI], 1.18–9.34) and crashing at nighttime (AOR = 4.28; 95% CI, 1.33–13.78) were significantly associated with increased injury severity among hospitalized motorcyclists.Conclusions: This study highlighted several high-risk behaviors among hospitalized motorcyclists in Vietnam. In addition, the study found that being unlicensed and crashing at night were associated with higher injury severity among hospitalized motorcyclists. The findings suggest that prevention and enforcement interventions targeting high-risk behaviors may reduce the significant morbidity and mortality associated with motorcycle crashes in Vietnam.