Well, as far as I'm concerned, YES, running sandboxed is secure, but I don't think you can ever say something is . . . "100%" secure. Sandboxie, though, is probably 99.9% secure. There are those that would argue that malware CAN in fact detect if it's in a sandbox (VM or Software Emulator), and indeed there have been some credible papers done on that.
While there has yet to be any credible evidence that malware can break out of a sandbox (I've heard it compared to waking up and realizing you are in jail, but you can't break out of jail), the malware writers I'm sure are hard at work figuring out a way to break out of a sandbox. And when sandboxes become more popular as security measures (and they are already being used by more and more people), no doubt the malware writers will increase their targeting efforts toward sandboxes.
Sandboxing is much less tedious than using a LUA . . . the only drawback is that when you try to do a download in a sandbox, the download is confined within the sandbox (which actually ISN'T a drawback if you happen to download malware) and the download is immediately deleted when you exit the sandbox session.
I consider that a drawback in the sense that if you don't remember you're in a sandbox and do a legitimate clean download, you have to start the download all over again in a non-sandboxed session. There is a sandbox marker ("[#]" for Sandboxie) up in the title bar and that will tell you the browser is in a sandbox (I'm in one right now), but I don't always look at the title bar. And then when I leave the sandboxed session and look for my download and see it's not there, that's when I go "Duhhhh . . ." and I have to do it all over again in a non-sandboxed session.
There IS a setting in Sandboxie that will allow a download to poke out of the sandbox, but once you start creating holes like that in the sandbox, you're defeating the whole purpose of the sandbox. That would be like leaving the jail door open.
Bottom line, sandboxes are secure right now, but as always the malware writers will figure out a way to "break out of jail".