Syncope in a worker undertaking risky tasks may result in fatalities for the individual or for third parties. We aimed at assessing the rate of syncope recurrence and the risk factors underlying the likelihood of syncope relapse in a working-age population. A prospective cohort of all patients aged 18–65 years consecutively admitted to the Emergency Department for syncope was enrolled. Risk of syncope relapse was assessed at a six-month, 1-year, and 5-year follow-up. Predictors of syncope recurrence have been evaluated at six months and 1 year from the syncope index by a multivariable logistic regression analysis. 348 patients were enrolled. Risk of syncope relapse was 9.2% at 6 months, 11.8% at 1 year, and 23.4% at 5 years. At 6-month follow-up, predictor of syncope recurrence was ≥3 prior lifetime syncope episodes. At 1-year, ≥3 prior lifetime syncope episodes, diabetes mellitus, and anaemia were risk factors for syncope relapse. There was an exceeding risk of recurrence in the first 6 months and a reduced risk of 3.5% per year after the first year. Anaemia, diabetes mellitus, and prior lifetime syncope burden are of importance when giving advice about the resumption of “high risk” jobs following a syncope episode.