Objective: Point-of-care (POC) D-dimer tests have been developed to exclude deep venous thrombosis quickly and on the spot, but are known to have lower sensitivity compared with laboratory-based tests. Their cost–effectiveness is still unknown. Methods: We updated and extended a previously published Markov model to assess the cost–effectiveness of POC D-dimer tests (‘Simplify’, ‘Cardiac’, ‘Triage’ and ‘Nycocard’) compared with a laboratory-based latex assay to diagnose deep venous thrombosis in primary care. Results: The ‘Laboratory’ strategy resulted in 6.986 quality-adjusted life years at the cost of €8354 per patient. All POC D-dimer tests resulted in health outcomes similar to the ‘Laboratory’ strategy. The ‘Simplify’ strategy maximized cost savings (–€155 [95% CI: –€246 to –€83]). Conclusions: POC D-dimer tests yield similar health outcomes as laboratory-based testing procedures but can be performed more easily and at lower costs. Therefore, these tests are an alternative to laboratory-based testing and might be considered for exclusion of deep venous thrombosis in primary care.