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Despite the burden of injury associated with motorcycle crashes and injuries in Vietnam, there are no studies investigating health-related quality of life (HRQoL) following a nonfatal motorcycle crash in this country. Therefore, this study aimed to evaluate the change of HRQoL preinjury, and at 6 and 12 months postinjury motorcycle crash in Ho Chi Minh City, Vietnam. Outcome measures were Physical Component Scores (PCS) and Mental Component Scores (MCS) of the Short Form 12 Health Survey (SF-12) version 2 and the EQ-5D. Multilevel mixed models were undertaken. A total of 352 hospitalized motorcyclists were followed-up. Compared with preinjury, the SF-12 PCS reduced by 6.61 points (95% confidence interval [CI] = −8.21 to −5.03) and 5.12 points (95% CI = −6.74 to −3.51) at 12 months postinjury. MCS also reduced by 4.23 points (95% CI = −5.99 to −2.47) at 6 months but increased by 1.29 points (95% CI = −0.49 to 3.08) at 12 months postinjury. The EQ-5D Visual Analogue Scale score decreased by 10.41 points (95% CI = −11.49 to −9.33) at 6 months and 6.48 points (95% CI = −7.58 to −5.38) at 12 months postinjury. The HRQoL among injured motorcycle riders improved between 6 and 12 months after injury but had not returned to the levels before injury.