OBJECTIVES: This study provides clinical researchers with guidance for determining the appropriateness of telephone versus face-to-face (F2F) interview methods when conducting patient-centered qualitative research to inform instrument development for use in regulated clinical trials.   METHODS: The benefits and limitations of telephone versus F2F interviews were identified from the peer-reviewed literature (N=15 studies) and discussed in the context of our own experiences conducting approximately 90 qualitative patient interview studies in the past five years.   RESULTS: Evidence suggests a variety of convenience benefits associated with telephone interviews (e.g., cost, access to patients) and that, overall, while some information is sacrificed (e.g., non-verbal communications), little to no data quality is lost when conducting interviews via telephone versus in-person.  However, experience suggests instances in which data quality between telephone and F2F interviews can vary dependent on purpose of interview and target patient population.  With respect to the purpose of the interview, telephone methods lend themselves best for concept elicitation, while in-person methods may be more suitable for cognitive debriefing, mode of administration equivalency, and usability testing.  With regard to target patient population, telephone methods may be appropriate for less vulnerable patient populations and/or well-defined disease areas, but less so for extremely sick or physically or emotionally compromised patients. CONCLUSIONS: Researchers developing instruments for use in regulated trials can consider telephone interviews viable for capturing qualitative patient data; however, the method’s suitability varies depending on the purpose of the interviews and the target patient population.  Additionally, some of the perceived “convenience” benefits of telephone interviews may not be fully realized when weighed against some surprising challenges inherent to their conduct including family members’ presence during interviews and frequent tardiness.  Practical guidance for the selection of interview mode is provided and solutions to address practical challenges associated with phone interviews are discussed.