Both Google and Python‘s style guide is the best practice:

if x is not None:
    # Do something about x

Using not x can cause unwanted results.

See below:

>>> x = 1
>>> not x
False
>>> x = [1]
>>> not x
False
>>> x = 0
>>> not x
True
>>> x = [0]         # You don't want to fall in this one.
>>> not x
False

You may be interested to see what literals are evaluated to True or False in Python:

• Truth Value Testing

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Edit for comment below:

I just did some more testing. not x is None doesn’t negate x first and then compared to None. In fact, it seems the is operator has a higher precedence when used that way:

>>> x
[0]
>>> not x is None
True
>>> not (x is None)
True
>>> (not x) is None
False

Therefore, not x is None is just, in my honest opinion, best avoided.

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More edit:

I just did more testing and can confirm that bukzor’s comment is correct. (At least, I wasn’t able to prove it otherwise.)

This means if x is not None has the exact result as if not x is None. I stand corrected. Thanks bukzor.

However, my answer still stands: Use the conventional if x is not None. :]

if not x is None is more similar to other programming languages, but if x is not None definitely sounds more clear (and is more grammatically correct in English) to me.

That said it seems like it’s more of a preference thing to me.

Code should be written to be understandable to the programmer first, and the compiler or interpreter second. The “is not” construct resembles English more closely than “not is”.

The is not operator is preferred over negating the result of is for stylistic reasons. “if x is not None:” reads just like English, but “if not x is None:” requires understanding of the operator precedence and does not read like english.

If there is a performance difference my money is on is not, but this almost certainly isn’t the motivation for the decision to prefer that technique. It would obviously be implementation-dependent. Since is isn’t overridable, it should be easy to optimise out any distinction anyhow.

The answer is simpler than people are making it.

There’s no technical advantage either way, and “x is not y” is what everybody else uses, which makes it the clear winner. It doesn’t matter that it “looks more like English” or not; everyone uses it, which means every user of Python–even Chinese users, whose language Python looks nothing like–will understand it at a glance, where the slightly less common syntax will take a couple extra brain cycles to parse.

Don’t be different just for the sake of being different, at least in this field.

Python if x is not None or if not x is None?

TLDR: The bytecode compiler parses them both to x is not None – so for readability’s sake, use if x is not None.

Readability

We use Python because we value things like human readability, useability, and correctness of various paradigms of programming over performance.

Python optimizes for readability, especially in this context.

Parsing and Compiling the Bytecode

The not binds more weakly than is, so there is no logical difference here. See the documentation:

The operators is and is not test for object identity: x is y is true
if and only if x and y are the same object. x is not y yields the
inverse truth value.

The is not is specifically provided for in the Python grammar as a readability improvement for the language:

comp_op: '<'|'>'|'=='|'>='|'<='|'<>'|'!='|'in'|'not' 'in'|'is'|'is' 'not'

And so it is a unitary element of the grammar as well.

Of course, it is not parsed the same:

>>> import ast
>>> ast.dump(ast.parse('x is not None').body[0].value)
"Compare(left=Name(id='x', ctx=Load()), ops=[IsNot()], comparators=[Name(id='None', ctx=Load())])"
>>> ast.dump(ast.parse('not x is None').body[0].value)
"UnaryOp(op=Not(), operand=Compare(left=Name(id='x', ctx=Load()), ops=[Is()], comparators=[Name(id='None', ctx=Load())]))"

But then the byte compiler will actually translate the not ... is to is not:

>>> import dis
>>> dis.dis(lambda x, y: x is not y)
  1           0 LOAD_FAST                0 (x)
              3 LOAD_FAST                1 (y)
              6 COMPARE_OP               9 (is not)
              9 RETURN_VALUE
>>> dis.dis(lambda x, y: not x is y)
  1           0 LOAD_FAST                0 (x)
              3 LOAD_FAST                1 (y)
              6 COMPARE_OP               9 (is not)
              9 RETURN_VALUE

So for the sake of readability and using the language as it was intended, please use is not.

To not use it is not wise.

I would prefer the more readable form x is not y
than I would think how to eventually write the code handling precedence of the operators in order to produce much more readable code.

Personally, I use

if not (x is None):

which is understood immediately without ambiguity by every programmer, even those not expert in the Python syntax.