Background: Efficacy has been proven for vortioxetine in short-term and long-term treatment of major depressive disorder (MDD), with broad beneficial effects on emotional, physical and cognitive symptoms. Limited specific data on the effects of vortioxetine on depression-related physical symptoms have been published. Methods: A meta-analysis was carried out of five short-term multinational, double-blind, placebo-controlled studies. These studies were conducted in a total of 2105 adult MDD outpatients (18–75 years) with a major depressive episode of ⩾3 months’ duration. Only patients treated with a dose of 5 or 10 mg vortioxetine (therapeutic doses) or placebo were included in this analysis. Efficacy assessment of vortioxetine on the physical symptoms of depression included all items of the Hamilton Depression Scale (HAM-D) assessing physical symptoms, and all somatic items in the Hamilton Anxiety Scale (HAM-A). A subgroup analysis in MDD patients with coexisting anxiety symptoms (i.e. those with a HAM-A ⩾20 at baseline) was also performed. Results: A significant improvement ( p<0.05) of vortioxetine versus placebo was observed on all HAM-D items measuring physical symptoms, except for the somatic gastrointestinal symptoms and loss of weight items. Significant effects were also observed on the HAM-A somatic items: general somatic symptoms, gastrointestinal symptoms, and autonomic symptoms. In patients with a high baseline level of anxiety, a significant effect of vortioxetine was also observed on the physical symptoms of depression. Conclusions: These analyses indicate that patients with MDD, including those with a high level of anxiety symptoms, have significant improvements in MDD-associated physical symptoms when treated with vortioxetine.