Objectives Bicyclists and motorcyclists contribute substantially to the morbidity and mortality rates of road crash casualties. The objective of the study was to investigate the crash characteristics of bicyclist and motorcyclist casualties presented to hospitals in Taiwan resulting from crashes. Methods By using linked data from The National Traffic Crash Dataset and the National Health Insurance Database between 2003 and 2012, logistic regression models were used to examine the determinants of hospitalisation among motorcyclist and bicyclist casualties. The examined variables include demographic characteristics, road and weather conditions, and vehicle characteristics. Results A total of 1,998,606 two-wheelers were enrolled in the study, of whom 216,600 were hospitalised: 203,623 were motorcyclists and 12,964 were bicyclists. Bicyclists were more likely to be hospitalised than motorcyclists were (14.0% vs. 10.7%). The pooled logistic regression model shows that bicyclists had higher odds of hospitalisation than motorcyclists (adjusted odds ratio [AOR] = 1.11, 95% confident interval [CI] = 1.08–1.14). In the motorcyclist and bicyclist models, helmet non-use appears to be a determinant of hospitalisation for motorcyclists (AOR = 1.14, CI = 1.12–1.16), although insignificant for cyclists (AOR = 1.03, CI = 0.94–1.12). Other important determinants of hospitalisation for motorcyclists and cyclists include female riders, elderly riders, rural roadways, unlicensed riding (for motorcyclists only), curved roadways, defective roadways, alcohol consumption (only for motorcyclists), and single-vehicle crashes (for motorcyclists only). Conclusions The result that bicyclists had an increased probability of being hospitalised than motorcyclists is particularly noteworthy, because there have recently been much more users of bikesharing systems in metropolitan cities where cycle helmets are not provided. We further found that helmet non-use was also a risk factor for motorcyclists, but insignificant for cyclists, possibly due to lower helmet utilization rates among bicyclists. Our findings regarding the increased hospitalisation percentage emphasize the importance of helmet use.