Depression is a major health problem and is not only underrecognized and undertreated but is associated with significant morbidity and mortality. Lavandula angustifolia Mill. (Lamiacae) is used to treat depression. Many medicinal plant textbooks refer to this indication, whereas there is no evidence-based document. Our objective was to compare the efficacy of tincture of L. angustifolia with imipramine in the treatment of mild to moderate depression and to evaluate the possible adjuvant effect of this tincture in a 4 week double-blind, randomized trial. Forty-five adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, for major depression based on the structured clinical interview for DSM IV participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. In this double-blind, single-center trial, patients were randomly assigned to receive lavandula tincture (1:5 in 50% alcohol ) 60 drops/day plus placebo tablet (Group A), tablet imipramine 100 mg/day plus placebo drop (Group B) and tablet imipramine 100 mg/day plus lavandula tincture 60 drops/day (Group C) for a 4-week study. In this small preliminary double-blind and randomized trial, lavandula tincture at this concentration was found to be less effective than imipramine in the treatment of mild to moderate depression (F=13.16, df=1, P=.001). In the imipramine group, anticholinergic effects such as dry mouth and urinary retention were observed more often that was predictable, whereas headache was observed more in the lavandula tincture group. A combination of imipramine and lavandula tincture was more effective than imipramine alone (F=20.83, df=1, P<.0001). As this study indicates, one of the advantages of this combination is a better and earlier improvement. The main overall finding from this study is that lavandula tincture may be of therapeutic benefit in the management of mild to moderate depression as adjuvant therapy. A large-scale trial is justified.