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Traumatic brain injury (TBI) is major contributor to the global burden of disease, especially in low- and middle- income countries, where most TBIs are traffic-related. Evidence shows that helmets protect against severe TBI. Cambodia continues to have the greatest motorcycle fatality rate in Southeast Asia. We investigated whether the National Motorcycle Helmet Law introduced in January 2016 had an impact on the epidemiology of motorcycle-related TBI in a neurosurgical referral center in Phnom Penh. This is a cross-sectional study of all patients admitted to the Department of Neurosurgery at Preah Kossamak Hospital with TBI following motorcycle accidents between January 2014 and December 2017. TBI admissions increased (from 234 in 2014 to 768 in 2017). The median age was 26 years, and most patients were male. The percentage of helmeted patients was 9% in 2014 and 13% in 2015; this increased to 18% in 2016, but dropped to 9% in 2017. Most TBIs occurred during the evening rush hour. Since 2016, more patients wore helmets in the daytime (up to 23%) than at night (5% between 1:00 and 5:00 am). Skull fracture, the most common pathology pre-law, decreased by 25% post-law (P < 0.001). With growing urbanization and motorization, TBI is a significant cause of morbidity and mortality in Cambodia. Two years after helmets became compulsory, most patients with TBI are still unhelmeted. Likely contributing factors are low penalty for noncompliance and inconsistent law enforcement. TBI is a major public health problem warranting further efforts to understand how to improve prevention strategies and advocate for change. [ABSTRACT FROM AUTHOR]