Background Collaborative care (CC) and consultation liaison (CL) are two conceptual models aiming to improve mental healthcare in primary care. The effects of these models have not been compared in a Danish setting. Aims To examine the effects of CC versus CL for persons with anxiety and depression in Danish general practices (trial registration: NCT03113175 and NCT03113201). Method Two randomised parallel superiority trials for anxiety disorders and depression were carried out in 2018-2019. In the CC-group, care managers collaborated with general practitioners (GPs) to provide evidence-based treatment according to structured treatment plans. They followed up and provided psychoeducation and/or cognitive-behavioural therapy. The GPs initiated pharmacological treatment if indicated, and a psychiatrist provided supervision. In the CL-group, the intervention consisted of the GP's usual treatment. However, the psychiatrist and care manager could be consulted. Primary outcomes were depression symptoms (Beck Depression Inventory-II, BDI-II) in the depression trial and anxiety symptoms (Beck Anxiety Inventory, BAI) in the anxiety trial at 6-month follow-up. Results In total, 302 participants with anxiety disorders and 389 participants with depression were included. A significant difference in BDI-II score was found in the depression trial, with larger symptom reductions in the CC-group (CC: 12.7, 95% CI 11.4-14.0; CL: 17.5, 95% CI 16.2-18.9; Cohen's d = -0.50, P ≤ 0.001). There was a significant difference in BAI in the anxiety trial (CC: 14.9, 95% CI 13.5-16.3; CL: 17.9, 95% CI 16.5-19.3; Cohen's d = -0.34, P ≤ 0.001), with larger symptom reductions in the CC-group. Conclusions Collaborative care was an effective model to improve outcomes for persons with depression and anxiety disorders.