To conduct an appropriate medical interview, education and clinical experience are necessary. The usefulness of computer-based medical diagnostic support systems has been reported in medical interviewing. However, only a few reports have actually applied these systems and noted changes in the quality of the medical interview of residents. We aimed to examine how the use of a medical interview support application changes the medical interviews of residents. The study was conducted on 15 residents (with less than two years post-graduation) and ran from November 2020 to March 2021. Faculty members played the role of simulated patients in 20 cases, and the residents conducted the medical interviews. In 10 of the 20 cases, a medical interview support application was used. After the interview, the residents were asked to list up to 10 differential diseases; the interview was considered appropriate if it included the disease portrayed by the simulated patient. Furthermore, the duration of the medical interview, the number of questions asked, and changes in stress parameters were evaluated. The use of a medical interview support application increased the percentage of appropriate medical interviews. Considering the frequency, the use of a medical interview support application increased the rate of appropriate medical interviews in the rare disease group, as well as the number of questions and duration of the interviews. No stress reduction was observed. The medical interview support application may be a useful tool in identifying appropriate differential diseases during medical interviews by residents.