In general cases, these acetals can be deprotected back to the aldehyde by using hydrochloric acid.

Trimethyl orthoformate is a useful building block for creating methoxymethylene groups and heterocyclic ring systems.

It introduces a formyl group to a nucleophilic substrate, e.g. RNH2 to form R-NH-CHO, which can undergo further reactions.

It is used in the production of some fungicides (for example: azoxystrobin and picoxystrobin), as well as for some members of the floxacin family of antibacterial drugs.

[4] Trimethyl orthoformate is also an effective reagent for converting compatible carboxylic acids to their corresponding methyl esters.