Venous thrombosis is a common and life-threatening disease that has received little attention in health psychology. The present study applied the theory of cognitive adaptation (TCA) to examine patients' reactions to venous thrombosis. Patients (N = 123) aged 16-84 recruited from anticoagulation units in the north of England completed measures of TCA constructs (meaning, mastery, self-esteem and optimism) and various outcome variables (anxiety, depression, thrombosis worries and quality of life) within 1 month of their thrombosis. The TCA explained large and significant amounts of variance in the outcome variables. In line with expectations, mastery, self-esteem and optimism were associated with positive adjustment. However, meaning was associated with elevated levels of distress. The results are discussed in relation to the search for meaning and the use of different control strategies in the early phases of adaptation to thrombosis.