I've been using MSE as my sole anti-virus software for three months now on two Windows laptops. One is running Vista business, the other is a netbook with 7 Starter. Before that, I was using Norton products, but when my subscription expired, I figured out that renewing was costly and so decided to give MSE a chance. (By the way, I'm still a big Norton fan.)
So can MSE replace Norton Anti-virus?
If you don't want to read through the rest, the short and simple answer is YES.
MSE indeed lives up to its promise of being a lightweight, hassle-free, top-notch anti-malware software. I don't know if this brings you any assurance, but at least I felt more secure knowing that MSE is based on the same protection technologies as Microsoft Forefront.
Microsoft Security Essentials main console
The installation was fuss-free and quick. Once installed, Windows Defender gets disabled, which is only natural since MSE is a superset of Defender. MSE's user interface is spartan, but extremely clear and well-organised. At one look you'll know if your system is healthy or not. Green means good, red means bad, yellow means at risk... couldn't be more straightforward.
Virus definition updating takes place either within the MSE console, or via Windows Update. You can update manually, or MSE will do it automatically in the background. There are new definitions released daily. It is really unobtrusive - no funny pop-up messages and what not - it just works.
Now the big question on every user's mind: is MSE effective in malware protection?
This I can't speak with authority, because everyone's mileage will vary. But I will say this: if you're a cautious user like me, then MSE is sufficient to keep you protected real-time from all the threats like worms, viruses, spyware, trojans etc.
Of course this gets tricky because 'cautious' is subjective and hard to define. What I mean by cautious includes not surfing dangerous websites, scanning files on download, running only programs you trust, scanning removable media before opening, doing weekly scans and so forth. If you're a careful computer user, and you don't intentionally do stuff that could harm your system, then MSE will keep you safe. But if you purposely visit malicious sites, install suspicious software, then I can't say with certainty MSE will protect you because I haven't been in that situation before.
All I can say is that in the three months, I have had zero virus attacks/infections using MSE as my only anti-virus. So to me, MSE is as good as Norton in protecting me from threats. Just today I plugged my friend's infected thumb drive into my computer, and immediately, MSE alerted me about the trojan before it even opened the contents. So from that one experience I can say real-time protection does work.
But surely MSE isn't perfect. There are areas which I felt could improve. Firstly, the scan times are quite long. I'm used to the super-quick quick scans from Norton products, so in comparison MSE's quick scan is noticeably longer. Also, full system scans may take anywhere between 1-2 hours depending your computer. It's a really long wait.
So to conclude, if you can't afford or don't want to pay for Norton anti-virus or similar products, I can safely recommend MSE to you and I'm sure it will keep your system safe and running. But of course if money is no issue then go get Norton, because Norton does have a few advantages and extra features. The real question is if these extras (like Norton file insight etc) are worth the money. That's only for you to decide. My advice is to first try out MSE, and if it isn't good enough then buy Norton. If it is, and for most people it will be, then keep on using MSE because it never expires!
It's hard to come across such good software. Microsoft has got anti-virus right. It's free, small, light and good. I never thought this day would come.

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