Antihypertensive drugs have been suggested to modulate symptoms of depression and anxiety. It is disputed whether this is due to the hypertension per se, its treatment, or both. The aim of this study was to investigate these associations in a large population sample. 55,472 participants in the Nord-Trøndelag Health Study (HUNT 2, 1995-1997), Norway, who completed the Hospital Anxiety and Depression rating Scale, were divided into 3 groups according to their diastolic blood pressure and antihypertensive treatment status. A cut-off of ≥90 mmHg diastolic blood pressure was used to identify hypertensive status. Differences in anxiety and depression symptom levels in untreated and treated hypertensives (all treatments) versus the normotensive reference group were explained by differences in age and gender distribution in the three groups in this study. However, the receipt of two or more antihypertensive drugs was associated with depressive symptoms alone (OR = 1.40, 95% CI = 1.03-1.90), but not with symptoms of anxiety (OR = 1.14, 95% CI = 0.83-1.57) or mixed anxiety and depression (OR = 1.19, 95% CI = 0.82-1.72) in the fully adjusted model, compared to untreated hypertension. Antihypertensive monotherapy (all agents) nor any single antihypertensive drug class were associated with symptoms of depression, anxiety, or mixed anxiety and depression. There may be a positive association between multi antihypertensive drug use and symptoms of depression, whereas this was not found in persons with symptoms of anxiety or mixed anxiety and depression. This might reflect poor antihypertensive treatment adherence leading to polypharmacy, or other unfavorable health behaviors in people with symptoms of pure depression.