Background: In a previous randomized cross-over study, patients perceived a physician delivering a more optimistic message as more compassionate and professional. However, the impact of the clinical outcome of patient on patients’ perception of physician’s level of compassion and professionalism has not been previously studied. Our aim was to determine if the reported clinical outcome modified the patient’s perception of physician compassion, professionalism, impression, and preference for physician. Methods: 128 advanced cancer patients in an outpatient Supportive Care Center were randomized to complete validated questionnaires about patients’ perception of physician’s level of compassion, professionalism, impression and preference of physician for themselves and their family after watching scripted videos depicting a physician delivering a more optimistic (MO) vs. a less optimistic (LO) message followed by a clinical vignette depicting a worse outcome. Results: Median age was 61 years and 55% were female. There was no difference in compassion score after the vignette for both the MO and LO groups respectively [mean difference (SD): 1.7(8.74) p = 0.4684 vs. 0.89(10.24) p = 0.1225] but there were worse overall impression [mean difference (SD): MO -0.79(1.62) p < 0.0001 vs. LO -1.17(1.91) p < 0.0001] and professionalism scores [MO -0.88(2.25) p = 0.0022 vs. LO -0.76(2.22) p = 0.0094]. In the MO group, preference for the physician for themselves [mean difference (SD) -0.29(0.77) p = 0.0049] and their family [mean difference (SD) -0.29(0.71) p = 0.0009] decreased after the vignette. Conclusions: Seeing a worse clinical outcome did not change the patients’ appraisal of an inappropriately optimistic physician. However, it reduced the overall impression of both physicians that conveyed a more or a less optimistic message and it also resulted in less likelihood of choosing the more optimistic physician for themselves and their family. Clinical trial information: NCT02498899