Objective To determine the effect of citalopram hydrobromide combined with conventional anti-heart failure therapy on the quality of life in the elderly patients with diastolic heart failure (DHF) and depression. Methods A total of 89 elderly DHF patients with depression admitted in our hospital from January 2014 to March 2015 were recruited in this study. According to their treatment, they were divided into citalopram hydrobromide group and amitriptyline hydrochloride group. On the basis of conventional anti-heart failure therapy, citalopram hydrobromide tablets were taken orally in the former group at 10-20 mg once, once to twice a day, with a daily dose not larger than 40 mg, and amitriptyline hydrochloride tablets were administered orally in the latter group at 25 mg once, twice to 3 times a day, with a daily dose no more than 300 mg (12 tablets), and maintenance dose of 50-150 mg (2 to 6 tables) for a continuous treatment for 8 weeks. Results Compared with before treatment, the value of left ventricular ejection fraction (LVEF) and the result of 6-minute walking test (6MWT) were improved after 8 weeks of treatment, the value of left ventricular end diastolic dimension (LVEDd) and score of Hamilton Depression Scale (HAMD) were decreased, and the scores of activities, daily life, health, recent support and general spirit were increased in the patients of both groups (P<0.05). Compared with the amitriptyline hydro-chloride group, the improvements of depression were more significant in the citalopram hydrobromide group (P<0.05). There was no significant difference in the incidence of adverse reactions between the 2 groups (Chi-square=0.362, P=0.547). Conclusion Citalopram hydrobromide combined with conventional anti-heart failure therapy can significantly attenuate the symptoms and improve the quality of life in the elderly DHF patients with depression.