Objectives The prevalence of neuropsychiatric symptoms in cognitively impaired nursing home residents is known to be very high, with depression and agitation being the most common symptoms. The possible effects of a 12-week intervention with animal-assisted activities (AAA) in nursing homes were studied. The primary outcomes related to depression, agitation and quality of life (QoL). Method A prospective, cluster randomized multicentre trial with a follow-up measurement 3 months after end of intervention was used. Inclusion criteria were men and women aged 65 years or older, with a diagnosis of dementia or having a cognitive deficit. Ten nursing homes were randomized to either AAA with a dog or a control group with treatment as usual. In total, 58 participants were recruited: 28 in the intervention group and 30 in the control group. The intervention consisted of a 30-min session with AAA twice weekly for 12 weeks in groups of three to six participants, led by a qualified dog handler. Norwegian versions of the Cornell Scale for Depression, the Brief Agitation Rating Scale and the Quality of Life in Late-stage Dementia scale were used. Results A significant effect on depression and QoL was found for participants with severe dementia at follow-up. For QoL, a significant effect of AAA was also found immediately after the intervention. No effects on agitation were found. Conclusions Animal-assisted activities may have a positive effect on symptoms of depression and QoL in older people with dementia, especially those in a late stage.