Background: Text-messaging interventions can reach many individuals across a range of socioeconomic groups, at a low cost. Few randomized controlled trials (RCTs) of text-messaging weight loss interventions have been conducted in United States., Methods: From September of 2016 to September of 2018, we conducted a two-parallel group, superiority, RCT of a 16-week text-messaging, weight loss intervention in Baltimore, Maryland, in overweight and obese adults younger than 71, who were able to receive text-messages. Our objective was to assess the effect of receiving the message content only (in printed documents distributed at baseline and week 8), versus receiving messages via short messaging service (SMS) on weight loss (primary outcome), body mass index, perceived exercise benefits and barriers, self-efficacy, and physical activity (PA). The random allocation sequence was equally balanced intervention groups by gender and age groups. Participants were randomized after the baseline assessment. Then, participants and most study staff were unblinded. Follow-up assessments were conducted at 8-, 16-, and 42-week post randomization. We performed intention-to-treat analysis using mixed linear regression models., Results: Of the 155 adults randomized (printed messages =77, SMS =78), 87.1% were women, 53.5% were African Americans, and 93.5% non-Hispanic. Participants who completed at least one follow-up assessment were included in regression analyses (n=145, printed messages =74, SMS =71). Compared to baseline, at the 42-week assessment, the average percent weight loss was 1.23 for the SMS group (P=0.006) and 0.86 for the printed messages group (P=0.047). Both groups experienced small reductions in weight (printed messages: -0.96 kg, P=0.022; SMS: -1.19 kg, P=0.006), BMI (printed messages: -0.32, P=0.035; SMS: -0.52, P=0.002), and percent energy from fat consumption (printed messages: -1.43, P=0.021; SMS: -2.14, P≤0.001). No statistically significant between groups differences were detected for any of the study outcomes. SMS response rates were not statistically significantly associated with study outcomes. No adverse events were reported., Conclusions: A semi-tailored SMS weight loss intervention among overweight and obese adults was not statistically superior in efficacy to paper-based messaging., Trial Registration: ClinicalTrials.gov Identifier: NCT04506996., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/mhealth-21-3). This study was funded by Lerner Center for Public Health Promotion, though which AYK, LF, TK, and KW salary support. The Lerner Center for Public Health Promotion was not involved in analysis or interpretation of the study results. AYK received doctoral training funding from the Johns Hopkins CLF-Lerner Fellowship, and a postdoctoral training grant from the National Institutes of Health (5T32HL129953-04). LH received NIH funding (MD012811, NR018916) and from the New York Regional Center for Diabetes Translation Research. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The other authors have no conflicts of interest to declare., (2022 mHealth. All rights reserved.)