Background A population-scale evidence for the association between moderate-to-vigorous physical activity (MV-PA) and risks of major adverse cardiovascular event (MACE) or all-cause mortality in people with various metabolic syndrome (MetS) status is warranted. Methods and Results We performed a nationwide retrospective cohort study based on the claims database of South Korea. We included people who received ≥3 national health screenings from 2009 to 2013 without a previous MACE history. We determined the MetS status of 6 108 077 people: MetS-chronic (N=864 063), MetS-developed (N=348 163), MetS-recovery (N=348 313), and MetS-free (N=4 547 538). The exposure was self-reported MV-PA frequencies. The outcome was incident MACEs or all-cause mortality. The incidence rate ratios (IRR) were calculated with adjustments for clinical/demographic characteristics. During the median follow-up of 4.28 years, 78 770 and 51 840 people experienced MACEs or died, respectively. Those who engaged in MV-PA had a significantly lower risk of MACEs or all-cause mortality than those not engaged in MV-PA in every spectrum of MetS. Even among those who were free from MetS (for MACEs, IRR 0.94 [0.92-0.97], for all-cause mortality, IRR 0.85 [0.82-0.87]) or who had already recovered from MetS (for MACEs, IRR 0.89 [0.84-0.95], for all-cause mortality, IRR 0.74 [0.68-0.81]), 1 to 2 days per week of MV-PA were significantly associated with lower risk of the adverse outcomes when compared with not being engaged in MV-PA. Those who were engaged in MV-PA more frequently also had significantly lower risks of MACEs or all-cause mortality. Conclusions This nationwide study suggests that MV-PA may be recommended to the general population regardless of recent MetS status.