Introduction: Non-adherence to antidepressants is common and limits the effectiveness of antidepressants. Pharmacists are in an ideal position to help patients cope with antidepressant treatment and, as experts in pharmacotherapy, can provide complementary skills to other health professionals. Pharmacists' interventions are effective in the improvement of adherence to antidepressants. However, little is known about the efficiency of such interventions. The study aimed to evaluate the cost-effectiveness and cost-utility of a community pharmacist intervention (CPI) in comparison with usual care (UC) in depressed patients initiating treatment with antidepressants in primary care. Methods: The economic evaluation was conducted alongside a randomized controlled trial with 6 months follow-up. Patients were recruited by general practitioners and randomized to CPI and UC. The intervention consisted of an educational programme focused on improving knowledge about medication, making patients aware of the importance of compliance, reducing stigma, reassuring World Congress on Integrated Care 2014, Sydney, November 23-26, 2014. International Journal of Integrated Care – Volume 14, 8 December – URN:NBN:NL:UI:10-1-116658– http://www.ijic.org/ patients about side-effects and stressing the importance of carrying out general practitioners' advice. Adherence to antidepressants, clinical symptoms, Quality-Adjusted Life-Years (QALYs), use of healthcare services and productivity losses were measured at baseline, 3 and 6 months. Results: A total of 179 patients were randomized to UC (92) and CPI (87). Although overall costs were higher in the CPI group than in UC patients, there were no significant differences between groups at baseline. From a societal perspective, the incremental cost-effectiveness ratio (ICER) was for the CPI compared with UC was €9,872 per extra QALY and €1,866 for extra adherent patient. In terms of remission of depressive symptoms, the UC dominated the CPI. If willingness to pay (WTP) is €30,000 per extra adherent patient, remission of symptoms or QALYs, the probability of the CPI being cost-effective was 0.71, 0.46 and 0.75, respectively from the societal perspective. From a healthcare perspective, the probability of the CPI being cost-effective in terms of adherence, QALYs and remission was of 0.71, 0.76 and 0.46, respectively, if WTP is €30,000. Discussion and conclusions: A low intensity CPI addressed to depressed patients initiating antidepressant treatment showed a probability of being cost-effective of 0.71 and 0.75 in terms of improvement of adherence and QALYs, respectively, when compared to IC. Regular implementation of the CPI is not recommended. Sample size calculation was based on the effectiveness analysis and the study could have been underpowered to detect differences. Only 74% of the patients in the CPI group received at least one intervention in the pharmacy and this may have limited its impact. A 6-month follow-up is a short period to evaluate long term costs and effects of the intervention. Future research needs to evaluate more complex and intensive pharmacist interventions in community pharmacy. It will be necessary to improve the collaborative relationship between the pharmacist and the practitioner, and the integration of the pharmacist into the primary care team. Also needed will be development of strategies that facilitate the attachment of the patient to the pharmacy and the establishment of a relationship between the pharmacist and the patient.