Abstract Background Understanding the characteristics of communication that foster patient-centered outcomes amid serious illness are essential for the science of palliative care. However, epidemiological cohort studies that directly observe clinical conversations can be challenging to conduct in the natural setting. We describe the successful enrollment, observation and data collection methods of the ongoing Palliative Care Communication Research Initiative (PCCRI). Methods The PCCRI is a multi-site cohort study of naturally occurring inpatient palliative care consultations. The 6-month cohort data includes directly observed and audio-recorded palliative care consultations (up to first 3 visits); patient/proxy/clinician self-report questionnaires both before and the day after consultation; post-consultation in-depth interviews; and medical/administrative records. Results One hundred fourteen patients or their proxies enrolled in PCCRI during Enrollment Year One (of Three). Seventy percent of eligible patients/proxies were invited to hear about a communication research study (188/269); 60 % of them ultimately enrolled in the PCCRI (114/188), resulting in a 42 % sampling proportion (114/269 eligible). All PC clinicians at study sites were invited to participate; all 45 participated. Conclusions Epidemiologic study of patient-family-clinician communication in palliative care settings is feasible and acceptable to patients, proxies and clinicians. We detail the successful PCCRI methods for enrollment, direct observation and data collection for this complex “field” environment.