Using data from two studies (Ns = 205 and 161), this article examines the associations between the domains of the five factor model of personality and hypochondriacal concerns (HCs). These associations are explored once covariation due to other related traits (somatosensory amplification) and comorbidity factors (anxiety, depression, and somatic symptom reporting) have been controlled. As predicted, emotional stability was associated with most criteria related to HCs and agreeableness was negatively associated with the perceived inadequacy of a physician’s explanation. Conscientiousness was negatively associated with HCs. These associations remained after partialing the comorbidity factors and somatosensory amplification. The discussion focuses on the particular role of agreeableness and conscientiousness in relation to HCs.