BACKGROUND: Human immunodeficiency virus (HIV) disease in the United States disproportionately affects minorities, including Latinos. Barriers including language are associated with lower antiretroviral therapy (ART) adherence seen among Latinos, yet ART and interventions for clinic visit adherence are rarely developed or delivered in Spanish. OBJECTIVE: The aim was to adapt a computer-based counseling tool, demonstrated to reduce HIV-1 viral load and sexual risk transmission in a population of English-speaking adults, for use during routine clinical visits for an HIV-positive Spanish-speaking population (CARE+ Spanish); the Technology Acceptance Model (TAM) was the theoretical framework guiding program development. METHODS: A longitudinal randomized controlled trial was conducted from June 4, 2010 to March 29, 2012. Participants were recruited from a comprehensive HIV treatment center comprising three clinics in New York City. Eligibility criteria were (1) adults (age ≥18 years), (2) Latino birth or ancestry, (3) speaks Spanish (mono- or multilingual), and (4) on antiretrovirals. Linear and generalized mixed linear effects models were used to analyze primary outcomes, which included ART adherence, sexual transmission risk behaviors, and HIV-1 viral loads. Exit interviews were offered to purposively selected intervention participants to explore cultural acceptability of the tool among participants, and focus groups explored the acceptability and system efficiency issues among clinic providers, using the TAM framework. RESULTS: A total of 494 Spanish-speaking HIV clinic attendees were enrolled and randomly assigned to the intervention (arm A: n=253) or risk assessment-only control (arm B, n=241) group and followed up at 3-month intervals for one year. Gender distribution was 296 (68.4%) male, 110 (25.4%) female, and 10 (2.3%) transgender. By study end, 433 of 494 (87.7%) participants were retained. Although intervention participants had reduced viral loads, increased ART adherence and decreased sexual transmission risk behaviors over time, these findings were not statistically significant. We also conducted 61 qualitative exit interviews with participants and two focus groups with a total of 16 providers. CONCLUSIONS: A computer-based counseling tool grounded in the TAM theoretical model and delivered in Spanish was acceptable and feasible to implement in a high-volume HIV clinic setting. It was able to provide evidence-based, linguistically appropriate ART adherence support without requiring additional staff time, bilingual status, or translation services. We found that language preferences and cultural acceptability of a computer-based counseling tool exist on a continuum in our urban Spanish-speaking population. Theoretical frameworks of technology's usefulness for behavioral modification need further exploration in other languages and cultures. TRIAL REGISTRATION: ClinicalTrials.gov NCT01013935; https://clinicaltrials.gov/ct2/show/NCT01013935 (Archived by WebCite at http://www.webcitation.org/6ikaD3MT7).