Although falls, cognitive impairments and mood disorders are very common in people with MS (PwMS) the relationship between these conditions has received scant attention. Therefore, the purpose of the study was to investigate the specific involvement of depression and anxiety on cognition and falls in PwMS. The study included 122 PwMS (75 women) divided into four subgroups according to their manifestation of depression and anxiety assessed by the Hospital Anxiety and Depression Scale (HADS) (i.e. no depression/no anxiety, depression/no anxiety, no depression/anxiety and depression/anxiety). Cognitive performance was evaluated via a computerized cognitive battery of tests. Participants were defined as "fallers" and "non-fallers" based on their fall history recorded during a clinical interview. Thirty-eight PwMS (31.1%) were classified as depressed (mean HADS 11.1, SD = 3.4); 52 (42.6%) were classified as anxious (mean HADS 11.1, S.D = 3.1) and 56 (45.9%) were neither depressed nor anxious. PwMS categorized in the anxiety/non-depressed subgroup were 6 times less likely to fall than PwMS without depression or anxiety (OR = 0.160, 95%CI = 0.040-0.646; P-value = 0.010). In terms of global cognitive status, depressed PwMS with anxiety were almost 4 times more likely to experience cognitive impairments compared to PwMS who were not depressed or anxious. Anxiety without comorbid depression is associated with less risk of falling, even when comparing MS patients without depression or anxiety. Future longitudinal investigations should confirm if this phenotype of MS patients with anxiety and without depression fall less compared with other mood groups.