The objective of the present study was to assess the effectiveness of a health advocate's casework with homeless people in a primary care setting in terms of improvements in health-related quality of life (QoL). The impact of the health advocacy intervention was assessed in a quasi-experimental, three-armed controlled trial. Homeless people moving into hostels or other temporary accommodation in the Liverpool 8 area of the UK and patients registering at an inner-city health centre as temporary residents were allocated in alternating periods to health advocacy (with or without outreach registration) or 'usual care' over a total intake period of 3 years. Health-related QoL outcomes were assessed using three independent self-report measures: the Life Fulfilment Scale; the Delighted-Terrible Faces Scale; and the Nottingham Health Profile. Out of the 326 homeless people who were given baseline questionnaires at registration, 222 (68%) returned usable questionnaires. Out of these individuals, 171 (77.0%) were traceable at follow-up, and 117 (68.4%) follow-up questionnaires were returned. The majority of respondents (n = 117) were women (72%) who were under 30 years of age (74%), white British (91%), and single (63%) or separated (23%), many of whom were living with their children (41%) in either women's refuges (30%) or family hostels (25%). Improvements in health-related QoL were greatest in people recruited and supported by a health advocate early in their stay in temporary housing, in comparison with those in the control group given 'usual care' at the health centre. The model of streamlined care for patients with complex psycho-social needs is shown to be a worthwhile and effective option for primary healthcare providers.