In enzymology, a Hydroxymethylglutaryl-CoA reductase (EC 1.1.1.88) is an enzyme that catalyzes the chemical reaction

(R)-mevalonate + CoA + 2 NAD⁺ ${\displaystyle \rightleftharpoons }$ 3-hydroxy-3-methylglutaryl-CoA + 2 NADH + 2 H⁺

The 3 substrates of this enzyme are (R)-mevalonate, CoA, and NAD⁺, whereas its 3 products are 3-hydroxy-3-methylglutaryl-CoA, NADH, and H⁺.

This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD⁺ or NADP⁺ as acceptor. The systematic name of this enzyme class is (R)-mevalonate:NAD⁺ oxidoreductase (CoA-acylating).^[1] Other names in common use include beta-hydroxy-beta-methylglutaryl coenzyme A reductase, beta-hydroxy-beta-methylglutaryl CoA-reductase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and hydroxymethylglutaryl coenzyme A reductase.