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Background Depression, anxiety, and at-risk drinking are highly prevalent in primary care settings. Many jurisdictions experience geographical barriers to accessing mental health services, necessitating the development and validation of alternative models of care delivery. Existing evidence supports the acceptability and effectiveness of providing mental health care by telephone. Objective This analysis assesses patient’s acceptability of computer-aided telephone support delivered by lay providers to primary care patients with depression, anxiety, or at-risk drinking. Methods The Primary care Assessment and Research of a Telephone intervention for Neuropsychiatric conditions with Education and Resources study is a randomized controlled trial comparing a computer-aided telephone-based intervention to usual care enhanced by periodic assessments in adult primary care patients referred for the treatment of depression, anxiety, or at-risk drinking; no part of the study involves in-person contact. For this analysis, the following data were obtained: reasons provided for declining consent; reasons provided for withdrawing from the study; study retention rate; and a thematic analysis of a satisfaction survey upon study completion. Results During the consent process, 17.1% (114/667) patients referred to the study declined to participate and 57.0% of them (65/114) attributed their refusal to research-related factors (ie, randomization and time commitment); a further 16.7% (19/114) declined owing to the telephone delivery of the intervention. Among the 377 participants who were randomized to the 1-year intervention, the overall retention rate was 82.8% (312/377). Almost no participants who withdrew from the study identified the telephone components of the study as their reason for withdrawal. Analysis of a qualitative satisfaction survey revealed that 97% (38/39) of comments related to the telephone components were positive with key reported positive attributes being accessibility, convenience, and privacy. Conclusions Our results suggest that a computer-aided telephone support is highly acceptable to primary care patients with depression, anxiety, or at-risk drinking. In particular, these patients appreciate its accessibility, flexibility, and privacy. Trial Registration ClinicalTrials.gov NCT02345122; https://clinicaltrials.gov/ct2/show/NCT02345122 (Archived by WebCite at http://www.webcitation.org/73R9Q2cle)