Many studies provide evidence for the so-called weekend effect by demonstrating that patients admitted to hospital during weekends show less favourable outcomes such as increased mortality, compared with similar patients admitted during weekdays. The underlying causes for this phenomenon are still discussed controversially. We analysed factors influencing weekend effects in inpatient care for acute stroke in Austria. The study analysed secondary datasets from all 130 public acute care hospitals in Austria between 2010 and 2014 (Austrian DRG Data). The study cohort included 86,399 patient cases admitted with acute ischaemic stroke. By applying multivariate regression analysis, we tested whether patient, treatment or hospital characteristics drove in-hospital mortality on weekends and national holidays. We found that the risk to die after an admission at weekend was significantly higher compared to weekdays, while the number of admissions following stroke was significantly lower. Adjustment for patient, treatment and hospital characteristics substantially reduced the weekend effect in mortality but did not eliminate it. We conclude that the observed weekend effect could be explained either by lower quality of health care or higher severity of stroke admissions at the weekend. In depth analyses supported the hypothesis of higher stroke severity in weekend patients as seen in other studies. While DRG data is useful to analyse stroke treatment and outcomes, adjustment for case mix and severity is essential.