Speaking as part of a BBC online documentary, released as part of National Air Ambulance Week, the father of two recalled: 'I think my most challenging one was to do with burns.'
'There's one job in particular that was really quite nasty and I don't know how the medical crew dealt with it either because they came to the rescue and did everything they (could) and sadly the casualty was beyond help.'
'Yeah, there are some very sad, dark moments and you know we talk about it a lot. That's the best way of dealing with some of the situations is you talk.'
William pictured on his first day as a helicopter pilot with Anglian Air Ambulance in July 2015
William and his captain, James Pusey, also discuss the importance of 'banter' at work, with the Duke saying: 'It helps de-stress and it also brings us together'.
'Because if you share the same, in some cases, sad incidents then, if you can get over it together, by being able to talk about it in the future, being a close team you come away with a collective way of dealing with it together and (it) helps you move on to whatever you've got to do next'.
He admits that initially he worried about people recognising him in the call of duty, but quickly found that he needn't have been concerned.
'Fortunately they don't really care who turns up as long as they're getting the care and the help that they need,' he explained.
'I have to say I was a little bit anxious of some of that when I first started, because I didn't want to bring any chaos or any sort of unhelpfulness to the scene. And, actually, it's worked out better than I could possibly have thought.'
William balances his role with his royal commitments and parenting George, three, and Charlotte, one
Whilst there are of course, difficult moments, William says that he thoroughly enjoys his role, which he successfully juggles with parenthood and his royal duties.
'It's rewarding when I come here to do this job and I really look forward to coming here every day, whether it's at 5.30am or going to bed at two in the morning. The shift work is still exciting and challenging for its variety more than anything and the fact that I love working in a team.'
'And that's something that my other job doesn't necessarily do. You're more out there on your own a little bit but I very much enjoy working with the likes of James and the team and it's good fun.'