Matsui won an overwhelming victory in Tuesday's special election, receiving 69 percent of the vote in a crowded field for the Sacramento-area seat.
A Washington lobbyist and former Clinton administration official, Matsui is the third California lawmaker's wife since 1998 to take over the seat of her deceased husband.
Santa Barbara-area Democrat Lois Capps succeeded her husband, Walter Capps.
Palm Springs Republican Mary Bono replaced her husband, Sonny Bono.
Matsui is expected to keep the her husband's office in the House Rayburn building.
She is the 45th congressional widow since 1923 to take a seat on Capitol Hill upon the death of her husband.
Bob Matsui died from a blood marrow disease after representing his state's capitol city for 26 years.
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