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Patients' first impressions obtained during early contacts with doctors represent the basis for relationship building processes. Aim of this study was to verify how patients' first impression of doctors' communication approach influences patients' global assessment of doctors' performance. This cross-sectional study was part of a larger, multicenter observational study aiming to assess lay-people's preferences regarding patient–doctor communication. All participants (N = 136) were equally distributed over two selected Italian and Dutch recruitment centers as well as for gender and age. In each center, panels of 6–9 persons each watched the same set of eight videotaped Objective Structured Clinical Examination consultations. Participants performed different tasks as to pick up salient communication elements while watching the videos and to rate doctors' global communicative performances on a 10-point Likert scale. We performed a mediation analysis to assess direct and indirect effects of participants' first impression on participants' global assessment. Among the 439 collected first impressions, 284(65%) were positive. When the first impression was positive, the mean value of the global assessment of doctors' performance was significantly higher (M = 7.4, SD = 1.5) than when the first impression was negative (M = 6.0, SD = 1.6); t(437) = 9.0 p <.001. According to the mediation analysis, this difference was due to a direct (c' = 0.53) and an indirect effect (ab = 0.86) deriving from the total effect of first impressions on the global assessment of doctors' performances (c = 1.39). In conclusion, the first impression has a strong impact on positive and negative judgments on doctors' communication approach and may facilitate or inhibit all further interactions. [ABSTRACT FROM AUTHOR]