I think a lot of it has to do with confidence. Both in yourself and your gear.
When I first started carrying I was very nervous about having a round chambered. As I became more comfortable with the idea and the firearm, I realized it had more to do with the holster I was using at the time. It was a plain (cheap) leather holster that didn't offer any retention. Once I got a decent Kydex holster I felt much more confident about safely carrying with one in the chamber as I wasn't afraid of the firearm falling out anymore. At first I carried with the safety on, but as time has gone by, I am now confident enough that it isn't going anywhere that I leave the safety off.
When I first started carrying I was very nervous about having a round chambered. As I became more comfortable with the idea and the firearm, I realized it had more to do with the holster I was using at the time. It was a plain (cheap) leather holster that didn't offer any retention. Once I got a decent Kydex holster I felt much more confident about safely carrying with one in the chamber as I wasn't afraid of the firearm falling out anymore. At first I carried with the safety on, but as time has gone by, I am now confident enough that it isn't going anywhere that I leave the safety off.