BACKGROUND: Gay, bisexual, and other men who have sex with men (MSM) are at elevated risk for acquiring sexually transmitted infections (STIs) in the United States, especially chlamydia and gonorrhea. While research has indicated main partners over casual partners may play a central role in STI risk, the frequency of STI screening among MSM couples is particularly low. Self-sample collection for chlamydia and gonorrhea screening has been shown to be highly accurate, and at-home STI testing has been shown to be highly acceptable among diverse populations. However, there is little research exploring the feasibility and acceptability of at-home chlamydia and gonorrhea screening among MSM couples. Our pilot study aims to help evaluate the viability of this screening modality as an intervention tool for MSM couples. OBJECTIVE: The objective of this study was to assess the feasibility and acceptability of an at-home chlamydia and gonorrhea sample collection and remote lab testing program among a sample of 50 MSM couples living in the United States. METHODS: This pilot study enrolled 50 MSM couples, ranging from 18-40 years old and living in the United States, who participated in a larger at-home HIV testing randomized controlled trial. Participating couples completed a pretest instructional video call and then had the option of completing at-home sample collection across three bodily sites (rectal swab, pharyngeal swab, and urine sample) for remote chlamydia and gonorrhea lab testing. For participants who completed any sample collection, they received their results via a posttest video call. All participants completed an online survey examining satisfaction and acceptability of the home testing process, experience with logistics, willingness to test at home in the future, recent sexual risk behavior, STI testing history, and linkage to care. A subset of 10 couples completed an in-depth interview about their attitudes towards the sample collection process, different decisions they made while collecting their samples, and their experience accessing treatment (for those who received a positive result). RESULTS: Recruitment began in September 2017, and as of March 2019 a total of 50 couples have been enrolled. Overall, 49/50 couples have returned their samples and completed the posttest delivery call, and 10 in-depth interviews have been completed and transcribed. CONCLUSIONS: Screening MSM couples at home for chlamydia and gonorrhea and providing video-facilitated results delivery may offer a tailored approach to address the increasing prevalence of these STIs. By collecting data on how MSM couples experience at-home STI screening, this project will provide valuable insight into the utility of such a service delivery program to public health interventionists and researchers alike. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/14481.