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Introduction: Despite the widespread availability of prevention of mother-to-child transmission (PMTCT) programs, many women in sub-Saharan Africa do not participate in PMTCT. This pilot study aimed to utilize partner participation in an intervention to support PMTCT uptake. Methods: Couples (n = 239) were randomized to receive either a comprehensive couples-based PMTCT intervention or the standard of care. Results: Compared to the standard of care, participants receiving the intervention increased HIV- and PMTCT-related knowledge ( F 1,474 = 13.94, p = .004) and uptake of PMTCT, as defined by infant medication dosing (74% vs. 46%, χ 2 = 4.69, p = .03). Discussion: Results indicate that increasing male attendance at antenatal clinic visits may be “necessary but not sufficient” to increase PMTCT uptake. Increasing HIV knowledge of both partners and encouraging active male participation in the PMTCT process through psychoeducational interventions may be a strategy to increase the uptake of PMTCT in South Africa.