In order to explore the clinical effects generated by the post-operative nursing and psychological comfort implemented for the patients with heart valve replacement surgery. In this study, select 50 patients receiving heart valve replacement surgery in recent one year from our hospital, and divide the patients into treatment group and control group by randomization method (each group contains 25 patients). Implement conventional nursing for 25 patients in control group, and implement post-operative nursing and psychological comfort for 25 patients in treatment group, and compare the treatment effects of two groups. The final result shown, after post-operative nursing and psychological comfort, the patients in treatment group realized an overall effective rate significantly higher than the control group; the Self-Rating Anxiety Scale (SAS) score of the treatment group was significantly lower than the control group, and the inter-group difference had statistical significance (P<0.05). Therefore, we came to the conclusion that taking reasonable and effective post-operative nursing measures and psychological comfort for the patients with heart valve replacement surgery, could effectively reduce the post-operative mortality rate and incidence of complications of the patients, reduce the anxious mood of the patient, is the key factor for success of heart valve replacement surgery and smooth recovery after the surgery, and is suitable for clinical promotion.