Background <p>As few as 20% of perinatal patients with depression or anxiety are treated to remission. Measurement-based care (MBC) improves patient outcomes but has not been evaluated for perinatal mental illness. We aimed to assess the feasibility of an MBC protocol in perinatal patients experiencing depression and/or anxiety symptoms.</p> Methods <p>In this pilot randomized controlled trial (RCT), perinatal people with Edinburgh Postnatal Depression Scale (EPDS) scores <i>≥</i> 13 were randomized 1:1 to (1) an electronic MBC (eMBC) intervention embedded in an electronic health record (EHR) that included scales assessing symptoms and functioning at each clinical visit or (2) usual care, for 12 weeks post-randomization. The primary outcome was feasibility (recruitment, acceptability, trial protocol adherence). While not powered to detect clinically significant differences on clinical outcomes, we also measured depressive and anxiety symptoms (Montgomery-Asberg Depression Rating Scale, MADRS; Hamilton Anxiety Scale, HAM-A).</p> Results <p>Of 42 participants (<i>n</i> = 21/arm), 32 (76.2%) completed follow-up questionnaires. At least one scale was completed in 87.5% of clinical encounters, but only 68.8% of encounters included documented participant-provider discussion of the results. Acceptability was good, with opportunities identified for improvement from participant and provider perspectives. At 12-weeks post-randomization, MADRS and HAM-A scores were non-signficantly lower in the eMBC group (mean differences: -1.10, 95%CI -7.81 to 5.61; -1.28, 95%CI -4.69 to 2.12).</p> Conclusions <p>The protocol evaluated in this study was feasible, which supports proceeding to a larger RCT to evaluate efficacy with minor modifications. If effective, an EHR-integrated eMBC intervention for perintal depression and anxiety could be implemented widely.</p> Trial registration <p>The trial was registered at <a href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</a> (NCT04836585). Registration Date: 08/04/2021.</p>