Introduction: Since Gagarin became the first human to travel into space and complete one orbit around the Earth, on 12 April 1961, the number of manned spaceflights has increased significantly. Spaceflight is still complex and has potential risk for incidents and accidents. The aim of this study was to analyze how safe it is for humans to travel in space. Objectives: This paper, therefore, summarizes incidents and accidents covering the six decades of manned spaceflight (1961–2020). Material and methods: Extensive PubMed, Cochrane, and Google Scholar searches were made with search strings of "incidents", "accident", "spaceflight", and "orbit", and including all vehicles so far. Search terms were combined by AND or OR in search strings. Of the results obtained, studies which evaluated manned spaceflight were included in the study. Data from the National Aeronautics Space Agency (NASA), the Russian Space Agency (ROSCOSMOS), the European Space Agency (ESA), and the Chinese Space Agency (CNSA), as well as from the Virgin Galactic and the SpaceX databases, were searched to complete data and to identify all the accomplished manned spaceflights, as well as all incidents and accidents that have occurred in the specific period. Search results were compared to findings on Wikipedia, Encyclopedia Astronautica, and other public webpages. Reference lists of included articles/homepages were also included for further potential data. Results: From 1961–2020, our data revealed an increasing number of manned space flights, n = 327. The number of times an astronaut has been sent to space, n = 1294, resulted in an accumulated n = 19,414 days spent in space. The number of days spent in orbit has constantly increased from 1961 until today. The number of incidents (altogether n = 36) and accidents (altogether n = 5) has constantly decreased. The number of astronauts who have died during spaceflight is represented by n = 19. The current statistical fatality rate is 5.8% (deaths per spaceflight) with the highest fatality rate in the 1960s (0.013 deaths/day spent in space), and the lowest rates in the 1990s and the period from 2010 until the present (no deaths). The most dangerous phases of spaceflight are launch, landing and staying in orbit. Altogether, n = 12 incidents (incident rate per spaceflight: 0.04) and one accident (accident rate: 0.003) during launch have been reported, n = 9 incidents (incident rate: 0.03) and two accidents (accident rate: 0.006) have been reported during landing and n = 10 incidents (incident rate: 0.03) have been reported in orbit. Discussion: Manned spaceflight over the last six decades has become significantly safer. Since 2003, no astronaut fatality has been reported. With greater international cooperation and maintaining of the International Space Station (ISS), the number of manned spaceflights and days spent in space has constantly increased, with constantly lower rates of incidents and accidents. [ABSTRACT FROM AUTHOR]