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This is very similar to this question but was not satisfactorily answered there.

It's very common for auto-checkers (e.g. Grammarly) to suggest a comma follow 'of course'.

For example, if I write "Of course I do", it underlines the word 'course' and suggests that it be changed to "Of course, I do".

But is that correct? It seems to me that "of course, I do" and "of course I do" could both be correct but mean something slightly different.

In the question linked above, user @HotLicks commented: Basic question: Do you pause anywhere when you say "Of course I don't"?

Possibly that was Socratically leading to the answer but I wanted to try to spell it out.

It seems to me that "Of course, I do" means something like, "on the other hand, this does apply to me." For example, I might say: "If I didn't have a bike, I wouldn't be able to ride to work. Of course, I do so I can."

On the other hand, "Of course I do!" means something like, "I am indignant that you would think that wouldn't apply to me." For example, I might say: "You think I don't have a bike? Of course I do!"

In the above paragraph, 'course' is underlined by Grammarly but the question is:

Is that really an illegitimate usage?

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Of course not.

Am I going to explain? Of course I am.

"Of course" has many uses. Sometimes it is used in a similar way to the word "obviously". It is in this context that it should be followed by a comma.

Of course, I will explain further.

Obviously, I will explain further.

In other contexts, "of course" is added for emphasis, in the way the word "definitely" might.

Of course not!

Definitely not!

When "of course" is used in the middle of a sentence, it is generally surrounded by parenthetical commas:

This, of course, is an example.

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    Sometimes the comma is just a matter of course. – Ian MacDonald Jan 29 at 19:39
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Usually I would use a comma, if the 'Of course' was introducing a contrary or alternative notion.

"The president is responsible for the actions of the Executive department, of course, our present president is an idiot."

Another way to look at it is to read it out loud. If you stop and pause after the '..course' then drop a comma.

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