Depression, anxiety, and Type-D pattern are associated with the earlier development and faster progression of cardiovascular disease (CVD). The aim of the randomized controlled PreFord trial was to improve multiple biological and psychosocial risk factors in the primary prevention of CVD. A total of 447 women and men with an ESC risk score >5% were randomly assigned to either multimodal or routine care groups. Somatic and psychosocial variables (HADS, DS-14) were assessed before and after the intervention, and annually for 2 years thereafter. The intervention showed no significant effects on the symptoms of depression, anxiety, and type D personality, either in the whole sample or in those with elevated scores at baseline. Thus, our study did not provide evidence that symptoms of depression, anxiety, or Type D personality can be effectively treated by multimodal behavioral interventions for the primary prevention of CVD.