Somatic symptom disorder (SSD) and illness anxiety disorder (IAD) are two new diagnoses introduced in the DSM-5. There is a need for reliable instruments to facilitate the assessment of these disorders. We therefore developed a structured diagnostic interview, the Health Preoccupation Diagnostic Interview (HPDI), which we hypothesized would reliably differentiate between SSD, IAD, and no diagnosis. Persons with clinically significant health anxiety (n = 52) and healthy controls (n = 52) were interviewed using the HPDI. Diagnoses were then compared with those made by an independent assessor, who listened to audio recordings of the interviews. Ratings generally indicated moderate to almost perfect inter-rater agreement, as illustrated by an overall Cohen's κ of .85. Disagreements primarily concerned (a) the severity of somatic symptoms, (b) the differential diagnosis of panic disorder, and (c) SSD specifiers. We conclude that the HPDI can be used to reliably diagnose DSM-5 SSD and IAD.