Pre-exposure prophylaxis (PrEP) can reduce the risk of HIV transmission among serodifferent couples trying to conceive, yet provider knowledge, attitudes, and experience utilizing PrEP for this purpose are largely unexamined. Trained interviewers conducted phone interviews with healthcare providers treating patients with HIV in seven cities (Atlanta, Baltimore, Houston, Kansas City, Newark, Philadelphia, and San Francisco, N = 85 total). Quantitative and qualitative data were analyzed to describe experience, concerns, and perceived barriers to prescribing PrEP for safer conception. Providers (67.1% female, 43 mean years of age, 70.4% white, 10 mean years treating HIV+ patients, 56% in academic vs. community facilities, 62.2% MD) discussed both benefits and concerns of PrEP for safer conception among serodifferent couples. Only 18.8% of providers reported experience prescribing PrEP, 74.2% were willing to prescribe it under ideal circumstances, and 7.0% were not comfortable prescribing PrEP. Benefits included added protection and a greater sense of control for the HIV-negative partner. Concerns were categorized as clinical, system-level, cost, or behavioral. Significant differences in provider characteristics existed across sites, but experience with PrEP for safer conception did not, p = 0.14. Despite limited experience, most providers were open to recommending PrEP for safer conception as long as patients understood the range of concerns and could make informed decisions. Strategies to identify and link serodifferent couples to PrEP services and clinical guidance specific to PrEP for safer conception are needed.