The presence of hope has been found to influence an individual's ability to cope with stressful situations. The objective of this study is to evaluate the relationship between medical errors, hope and burnout among practicing physicians using validated metrics. Prospective cohort study was conducted among hospital based physicians practicing in Japan (N = 836). Measures included the validated Burnout Scale, self-assessment of medical errors and Herth Hope Index (HHI). The main outcome measure was the frequency of self-perceived medical errors, and Poisson regression analysis was used to evaluate the association between hope and medical error. A total of 361 errors were reported in 836 physician-years. We observed a significant association between hope and self-report of medical errors. Compared with the lowest tertile category of HHI, incidence rate ratios (IRRs) of self-perceived medical errors of physicians in the highest category were 0.44 (95%CI, 0.34 to 0.58) and 0.54 (95%CI, 0.42 to 0.70) respectively, for the 2(nd) and 3(rd) tertile. In stratified analysis by hope score, among physicians with a low hope score, those who experienced higher burnout reported higher incidence of errors; physicians with high hope scores did not report high incidences of errors, even if they experienced high burnout. Self-perceived medical errors showed a strong association with physicians' hope, and hope modified the association between physicians' burnout and self-perceived medical errors.