It has long been established that pilot fatigue can present a risk to flight safety - a risk that needs to be managed at company, national and European level (see also "Proof that Fatigue Kills" - PDF).
Safety experts reckon that pilot fatigue contributes to 15-20% of fatal aviation accidents caused by human error. They also establish an increased probability of a human factor accident the longer pilots are on duty, especially for duty periods of 13 hours and above (see following statements):
"It is estimated (e.g. by the NTSB) that fatigue contributes to 20-30% of transport accidents (i.e. air, sea, road, rail). Since, in commercial aviation operations, about 70% of fatal accidents are related to human error, it can be assumed that the risk of the fatigue of the operating crew contributes about 15-20% to the overall accident rate. The same view of fatigue as a major risk factor is shared by leading scientists in the area, as documented in several consensus statements." See Akerstedt, T., Mollard, R., Samel, A., Simons, M., Spencer, M. (PDF) The role of EU FTL legislation in reducing cumulative fatigue in civil aviation.
"For 10-12 hours of duty time the proportion of accident pilots with this length of duty period is 1.7 times as large as for all pilots. For pilots with 13 or more hours of duty, the proportion of accident pilot duty periods is over five and a half times as high. [...] 20% of human factor accidents occurred to pilots who had been on duty for 10 or more hours, but only 10% of pilot duty hours occurred during that time. Similarly, 5% of human factor accidents occurred to pilots who had been on duty for 13 or more hours, where only 1% of pilot duty hours occur during that time. There is a discernible pattern of increased probability of an accident the greater the hours of duty time for pilots." See Goode, J. H. Are pilots at risk of accidents due to fatigue? (PDF). Federal Aviation Administration, Office of Aviation Policy and Plans, Washington, DC 20591, USA, March 2003.
Recent examples of pilot fatigue endangering the safety of passengers are the serious incident in Iceland (in 2007 – see next subsection), the Colgan Air accident in the US in 2009 (50 people killed – see America Acts on Pilot Fatigue) and the Air India crash in 2010 (158 dead).