AbstractPeople experiencing homelessness report increased exposure to traumatic life events and higher rates of depression, anxiety, and post‐traumatic stress disorder as compared with the general population. Heart rate variability‐biofeedback (HRV‐BF) has been shown to decrease symptoms of stress, anxiety, depression, and PTSD. However, HRV‐BF has not been tested with the most vulnerable of populations, homeless adults. The purpose of this randomized controlled trial was to compare the effectiveness of an HRV‐BF intervention versus a Health Promotion (HP) active control intervention focused on improving mental health symptoms among homeless adults. Guided by a community advisory board, homeless adults residing in Skid Row, Los Angeles (n = 40) were randomized to either the HRV‐BF or an active HP control group and received eight weekly, 30‐min sessions over two months, delivered by a nurse‐led community health worker team. Dependent variables of HRV, mental health, anxiety, depression, and PTSD were measured at baseline, the 8‐week session, and/or 2‐month follow‐up. All intervention sessions were completed by 90% (36/40) of participants. Both the HRV‐BF and HP interventions showed significant increases in HRV from baseline to 2‐month follow‐up, with no significant difference between the intervention groups. The HRV‐BF programme revealed a somewhat greater, although non‐significant, improvement in anxiety, depression, and PTSD symptoms than the HP programme. The usefulness of both interventions, focused on emotional and physical health, warrants future studies to examine the value of a combined HRV‐BF and HP intervention.