Introduction: The management of long-term physical conditions is a challenge worldwide, absorbing a majority resources despite the importance of acute care. The management of these conditions is done largely in primary care and so interventions to improve primary care could have an enormous impact. However, very little data exist on how to do this. Mental distress is frequently comorbid with long term physical conditions, and can impact on health behaviour and adherence, leading to poorer outcomes. DIALOG+ is a low-cost, patient-centred and solution-focused intervention, which is used in routine patient-clinician meetings and has been shown to improve outcomes in mental health care. The question arises as to whether it could also be used in primary care to improve the quality of life and mental health of patients with long-term physical conditions. This is particularly important for low- and middle-income countries with limited health care resources. Methods: An exploratory non-controlled multi-site trial was conducted in Bosnia and Herzegovina, Colombia, and Uganda. Feasibility was determined by recruitment, retention, and session completion. Patient outcomes (quality of life, anxiety and depression symptoms, objective social situation) were assessed at baseline and after three approximately monthly DIALOG+ sessions. Results: A total of 117 patients were enrolled in the study, 25 in Bosnia and Herzegovina, 32 in Colombia, and 60 in Uganda. In each country, more than 75% of anticipated participants were recruited, with retention rates over 90% and completion of the intervention exceeding 92%. Patients had significantly higher quality of life and fewer anxiety and depression symptoms at post-intervention follow-up, with moderate to large effect sizes. There were no significant improvements in objective social situation. Conclusion: The findings from this exploratory trial suggest that DIALOG+ is feasible in primary care settings for patients with long-term physical conditions and may substantially improve patient outcomes. Future research may test implementation and effectiveness of DIALOG+ in randomized controlled trials in wider primary care settings in low- and middle-income countries. Trial registration: All studies were registered prospectively within the ISRCTN Registry. ISRCTN17003451, 02/12/2020 (Bosnia and Herzegovina), ISRCTN14018729, 01/12/2020 (Colombia) and ISRCTN50335796, 02/12/2020 (Uganda).