With Ole-Johan Dahl, he developed the initial ideas for object-oriented programming (OOP) in the 1960s at the Norwegian Computing Center (Norsk Regnesentral (NR)) as part of the Simula I (1961–1965) and Simula 67 (1965–1968) simulation programming languages, which began as an extended variant and superset of ALGOL 60.

In 2004, the Association Internationale pour les Technologies Objets (AITO) established an annual prize in the name of Ole-Johan Dahl and Kristen Nygaard to honor their pioneering work on object-orientation.

He conducted research for Norwegian trade unions on planning, control, and data processing, all evaluated in light of the objectives of organised labour (1971–1973), working together with Olav Terje Bergo.

Starting in 1976, he was engaged in developing and (since 1986) implementing the general object-oriented programming language BETA, together with Bent Bruun Kristensen, Ole Lehrmann Madsen, and Birger Møller-Pedersen.

Also in the 1980s, he was chairman of the steering committee for the Cost-13 (European Common Market Commission)-financed research project on the extensions of profession-oriented languages necessary when artificial intelligence and information technology are becoming part of professional work.

He was the leader of General Object-Oriented Distributed Systems (GOODS), a three-year Norwegian Research Council-supported project starting in 1997, aiming at enriching object-oriented languages and system development methods by new basic concepts that make it possible to describe the relation between layered and/or distributed programs and the computer hardware and people carrying out these computer programs.

Nygaard's final research interests were studies of the introductory teaching of programming, and creating a process-oriented conceptual platform for informatics.

These subjects are to be developed in a new research project named Comprehensive Object-Oriented Learning (COOL), together with several international test sites.

In November 1999, he became chair of an advisory committee on Broadband Communication for the Norwegian Department for Municipal and Regional Affairs.

In 1999, he and Dahl became the first people to receive the then new Rosing Prize, awarded by the Norwegian Data Association for exceptional professional achievements.

He was for 10 years (in the 1970s) Norwegian representative in the Organisation for Economic Co-operation and Development (OECD) activities on information technology.

In the referendum on 28 November 1994, "Nei til EU" succeeded: 52.2% of the electorate voted "No", and the voter participation was the highest ever in Norway's history: 88.8%.

She specialized for a number of years in recruiting and giving administrative support to specialists working in East Africa.