Objectives: To assess whether specific factors predict the development of ManuScript Rejection sYndrome (MiSeRY) in academic physicians. Design: Prospective pilot study; participants self-administered a questionnaire about full manuscript submissions (as first or senior author) rejected at least once during the past 5 years. Setting: Single centre (tertiary institution). Participants: Eight academic physician-authors. Main outcome measures: Duration of grief. MiSeRY was pre-specified as prolonged grief (grief duration longer than the population median). Results: Eight participants provided data on 32 manuscripts with a total of 93 rejections (median, two rejections per manuscript; interquartile range [IQR], 1–3 rejections per manuscript). Median age at rejection was 37 years (IQR, 33–45 years); 86% of 80 rejections involved male authors (86%), 56 of the authors providing data about these rejections were first authors (60%). The median journal impact factor was 5.9 (IQR, 5.2–17). In 48 cases of rejection (52%), pre-submission expectations of success had been high, and in 54 cases (58%) the manuscripts had been sent for external review. Median grief duration was 3 hours (IQR, 1–24 h). Multivariate analysis indicated that higher pre-submission expectation (adjusted odds ratio [aOR], 5.0; 95% CI, 1.5–18), first author status (aOR, 9.5; 95% CI, 1.1–77), and external review (aOR, 19.0; 95% CI 2.9–126) were independent predictors of MiSeRY. Conclusions: To help put authors out of their MiSeRY, journal editors could be more selective in the manuscripts they send for external review. Tempering pre-submission expectations and mastering the Coping and reLaxing Mechanisms (CaLM) of senior colleagues are important considerations for junior researchers.