Neopentyl glycol (NPG) synthesis by condensation disproportionation of formaldehyde and isobutyraldehyde (IBD) with sodium hydroxide as catalyst was studied in a continuous‐flow microreactor under various experimental conditions, such as reaction temperature, residence time, and the molar ratio of reactants. All the conditions were determined by Box‐Behnken experimental design and the response surface method based on the preferred range selected by single‐factor experiments. For comparison, NPG was synthesized by condensation disproportionation of the same reactants in a batch reactor. The results showed that higher NPG yield and shorter residence time were achieved in a continuous‐flow microreactor than in a batch reactor when the other experimental conditions were similar.