His many years of success in legal practice, .............. , didn't come out without challenges

Analyze the question

The sentence is: "His many years of success in legal practice, .............. , didn't come out without challenges."

The blank sits between two commas, so it must be a word or phrase that can be inserted as a parenthetical (an interrupter) without breaking the sentence. The sentence must still work grammatically if the blank is removed: "His many years of success in legal practice didn't come without challenges."

Concept: parenthetical expressions

Words like however, indeed, therefore, moreover can be inserted in the middle of a sentence and set off by commas. Conjunctions such as but join clauses and are not set off like this. Prepositional phrases like in spite of all need a noun to complete them, and "in spite of all, ..." leaves a dangling fragment in this position.

Test each option

• A. but: "...legal practice, but, didn't come..." The conjunction but needs to join two clauses. Here there is no clause before it, so this is wrong.
• B. in spite of all: This is a preposition phrase that needs an object (in spite of all the odds). It would also contradict the structure, so it is wrong.
• C. indeed: "...legal practice, indeed, didn't come out without challenges." It fits grammatically, but indeed means "in fact" and reinforces. It does not show contrast with the idea of success. The sentence is about success that nonetheless had challenges, so a contrast word is more logical.
• D. However: "His many years of success in legal practice, however, didn't come out without challenges." This is a correct parenthetical that signals contrast between success and difficulties. It fits perfectly.

Note on the capital letter: The option is written "However" with a capital H only because it is the start of an option. In the sentence it would be lowercase (however).

Answer

The correct option is D. However.

Tip: When a blank is enclosed by two commas, look for a parenthetical word (however, therefore, indeed, moreover) and choose the one that matches the meaning. Contrast in the sentence (success vs. challenges) points to however.