Introduction Many professional football players sustain at least one severe injury over the course of their career. Because detailed epidemiological data on different severe injuries in professional football have been missing so far, this study describes the frequency and return-to-competition (RTC) periods of different types of severe football injuries. Material and methods This epidemiological investigation is a prospective standardised injury analysis based on national media longitudinal registration. Injuries were classified according to the consensus statement by Fuller et al. (2006). The analysis includes injuries sustained by players of the first German football league during the seasons 2014-2015 to 2017-2018. Level of evidence: II. Results Overall, 660 severe injuries were registered during the four seasons (mean 165 per season; 9.2 per season per team; incidence in 1000 h: 0.77). The body region most frequently affected by severe injury was the knee (30.0%; 49.5 injuries per season/SD 13.2) followed by the thigh (26.4%; 43.5 injuries/SD 4.2) and the ankle (16.7%; 27.5 injuries/SD 5.0). The distribution of injuries over the course of a season showed a trend for ACL ruptures to mainly occur at the beginning of a season (45.8%), overuse syndromes such as achillodynia (40.9%) and irritation of the knee (44.4%) during the winter months and severe muscle and ankle injuries at the end of a season. ACL ruptures showed the longest RTC durations (median 222 days). Conclusion This study presents detailed epidemiological data on severe injuries in professional football. The body region most frequently affected by severe injuries was the knee. Several types of severe injuries showed a seasonal injury pattern. The appropriate timing of RTC after an injury is one of the most important and complex decisions to be made. This study provides information on the typical time loss due to specific severe football injuries, which may serve as a guideline.