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Background: Detection of perinatal depression by healthcare providers remain an important barrier to receiving treatment. This study reports on the detection of perinatal depression by frontline non-physician primary healthcare workers (PHCWs) as well as the feasibility, effectiveness and acceptability of routine screening using the 2-item patient health questionnaire (PHQ-2) during antenatal care., Method: Twenty-seven primary healthcare facilities were assigned to screening (n = 11) and non-screening (n = 16) arms. All PHCWs in both arms were trained to diagnose and treat perinatal depression using the WHO mental health gap action intervention guide (mhGAP-IG) while those in the screening arm were trained to routinely screen with PHQ-2 first to determine need for further mhGAP-IG assessment. Perceived usefulness, feasibility and acceptability of routine screening for perinatal depression was explored in key informant interviews on a purposive sample of PHCWs (n = 20) and study participants (n = 22)., Results: In the first 6-months following training, the detection rate of perinatal depression was 4.6% at the clinics where PHCW were not routinely screening with the PHQ-2 compared to 11% at the screening clinics. Over the next six months, with refresher training for PHCW in the screening arm and the introduction of monthly supportive supervision for PHCW in both arms, detection rates increased from 4.6 to 7.6% at non-screening clinics and from 11 to 40% at the screening clinics. Over the entire study period only 81 (15.7%) out of the 517 cases of perinatal depression were detected by the PHCWs. Detection of depression by PHCWs was associated with the severity of depression symptoms and routine screening with PHQ-2. The introduction of routine screening was acceptable to both PHCWs and perinatal women. PHCWs reported that the PHQ-2 was useful, easy to administer and feasible for routine use., Conclusions: Improving detection and subsequently the treatment gap for perinatal depression require not just training of frontline healthcare workers but the introduction of additional measures such as universal screening along with supportive supervision., Trial Registration Number: The main study from which the data for this report was extracted was retrospectively registered 03 December 2019., Registration Number: ISRCTN 94,230,307., Competing Interests: Declarations. Ethics approval and consent to participate: Written informed consent was obtained from all participants. All procedures involving human subjects/patients for the SPECTRA study were approved by the University of Ibadan and University College Hospital Ethics Committee (approval number- UI/EC/16/0003). Additional ethics approval was obtained to use the data emanating from the SPECTRA study for a doctorate degree. The protocol: Integrating care for perinatal depression in primary care: an implementation study (adapted from the SPECTRA study protocol) was approved by the University of Stellenbosch Health Research Ethics Committee HREC Reference No: S21/04/074 (PhD). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)