In 1940, Vian met Michelle Léglise, who became his wife in 1941. She taught Vian English and introduced him to translations of American literature. Also in 1940 Vian met Jacques Loustalot, who became a recurring character in several early novels and short stories as "the colonel". Loustalot died accidentally in 1949 falling from a building he was trying to climb on in order to enter into a flat by the window, after a bet. In 1942 Vian and his brothers joined a jazz orchestra under the direction of Claude Abbadie, who became a minor character in Vian's Vercoquin et le plancton. The same year Vian graduated from École Centrale with a diploma in metallurgy and also in 1942 Boris and Michelle's son Patrick was born.
The year 1948 saw the birth of Vian's daughter, Carole. He continued his literary career by writing Vernon Sullivan novels, and also published poetry collections: Barnum's Digest (1948) and Cantilènes en gelée (Cantelinas in Jelly) (1949). Vian also started writing plays, the first of which, L'Équarrissage pour tous (Slaughter for Everyone), was staged the year it was written, 1950. The same year saw publication of Vian's third major novel, L'Herbe rouge (The Red Grass). This was a much darker story than its predecessors, centering around a man who built a giant machine that could help him psychoanalyse his soul. Like the other two books, it did not sell well; Vian's financial situation had been steadily worsening since late 1948, and he was forced to take up translation of English-language literature and articles to get by. Vian separated from his wife, and in 1950 he met Ursula Kübler (1928–2010), a Swiss dancer; the two started an affair, and in 1951 Vian divorced Michelle. Ursula and Boris married in 1954.