Heterosexual transmission of HIV often occurs in the context of intimate sexual partnerships. There is mounting evidence that couple-based HIV prevention interventions may be more effective than individual-based interventions for promoting risk reduction within such relationships. Yet, concerns have been raised about the safety of couple-based prevention approaches, especially with regard to the risk of intimate partner violence against women. Although several international studies have examined the potential for adverse consequences associated with couple-based interventions, with inconsistent results, there is little data from U.S. studies to shed light on this issue. The current study analyzed data from a randomized trial conducted in New York City with 330 heterosexual couples to examine whether participation in couple-based or relationship-focused HIV counseling and testing (HIV-CT) interventions resulted in an increased likelihood of post-intervention breakups, relationship conflicts, or emotional, physical, or sexual abuse, compared with standard individual HIV-CT. Multinomial logistic regression was used to model the odds of experiencing change in partner violence from baseline to follow-up by treatment condition. A high prevalence of partner-perpetrated violence was reported by both male and female partners across treatment conditions, but there was no conclusive evidence of an increase in relationship dissolution or partner violence subsequent to participation in either the couple-based HIV-CT intervention or relationship-focused HIV-CT intervention compared with controls. Qualitative data collected from the same participants support this interpretation. HIV prevention interventions involving persons in primary sexual partnerships should be sensitive to relationship dynamics and the potential for conflict, and take precautions to protect the safety of both male and female participants.