BACKGROUND: Couples HIV testing and counseling (CHTC) is now a standard of care prevention strategy recommended by the Centers for Disease Control and Prevention for sexual minority men (SMM) in relationships. Despite standard recommendations that couples complete CHTC every 6-12 months, no study has empirically evaluated the effects associated with CHTC retesting. OBJECTIVE: This study aims to understand the benefits associated with continued dyadic engagement in the HIV prevention continuum through routine CHTC retesting, which is of particular importance for emerging-adult SMM in relationships who use drugs. METHODS: Eligible couples for this CHTC retesting trial must already be enrolled in the 4Us trial, where they completed a CHTC session after their baseline survey. The purpose of the original 4Us trial was to test the efficacy of 2 intervention components for CHTC: a communication skills training video and a substance use module. Couples were eligible for the original 4Us trial if they identified as cisgender male, were in a relationship for 3 months or longer, were aged 17 years or older, and communicated in English. At least 1 partner had to be aged 17-29 years, report HIV negative or unknown serostatus, report use of at least 1 drug (cannabis, cocaine or crack, crystal methamphetamine, ketamine, gamma-hydroxybuterate [GHB], psychedelics, ecstasy, prescription medication misuse, opiates, and nitrates) use, and engage in condomless anal sex (CAS) acts with a casual partner or have a main partner who is nonmonogamous or serodiscordant. Those who complete the 4Us 12-month follow-up and remain in a relationship with the partner they participated in 4Us with are offered the opportunity to participate in this CHTC retesting trial. Those consenting are randomized to either CHTC retesting or individual HIV testing. Follow-up assessments are conducted 3 and 6 months after randomization to evaluate the effects of repeat CHTC on 2 primary outcomes: (1) CAS with a casual partner in the absence of preexposure prophylaxis (PrEP), and (2) CAS with a serodiscordant main partner who is not virally suppressed or concurrent CAS between main and casual partners in the absence of PrEP. RESULTS: The CHTC retesting trial launched in January 2023, and enrollment is ongoing. As of February 2024, the study had enrolled 106 eligible participants (n=53 couples). CONCLUSIONS: Findings from this CHTC retesting study will contribute to knowledge about the benefits associated with regular (repeated) CHTC testing versus routine individual HIV testing for SMM in relationships. The results of this trial will inform CHTC retesting guidance. TRIAL REGISTRATION: ClinicalTrials.gov NCT05833074; htps://www.clinicaltrials.gov/study/NCT05833074. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53023.