Objective Recurrent disease flare is one of the key problems in lupus patients. A Chinese Flare-Prevention Lupus Initiative Cohort (FLIC) was established. Risk factors of disease flare were evaluated accordingly.Methods Patients with low-grade disease activity (the Safety of Estrogens in Lupus Erythematosus National Assessment–SLE Disease Activity Index (SELENA-SLEDAI) =≤6, daily prednisone ≤20 mg, no British Isles Lupus Assessment Group A or no more than one B organ domain score) from January 2014 to August 2020 were included in the FLIC. Disease flares were defined by the modified SELENA-SLEDAI Flare Index. Low disease activity status (LDAS) and remission were also assessed. The cumulative flare rate was estimated by an event per 100 person-years analysis. Cox proportional hazards models were performed to identify risk factors of subsequent disease flares after adjusting clinical confounders. Survival was assessed with the Kaplan-Meier method.Results 448 eligible patients with low-grade disease activity were included in FLIC. During a mean follow-up of 30.4 months, 170 patients flared. The cumulative lupus flare rate was 22.2 events per 100 patient-years. Compared with patients without flare, those with lupus flares were taking more prednisone, had higher disease activity index and with less patients attained LDAS/remission at baseline. They also had higher rates of antiphospholipid antibodies (aPLs) and antiribosomal P antibody. Cox regression analysis confirmed that attainment of either LDAS or remission at baseline were independent protective factors against subsequent disease flare (LDAS but not in remission: HR 0.58, 95% CI 0.38~0.88; remission: HR 0.46, 95% CI 0.30~0.69), while aPL was a risk factor of lupus flares (HR 1.95, 95% CI 1.36~2.78). Kaplan-Meier curves indicated that attaining LDAS or remission and absence of aPL at baseline had the least flare risk.Conclusions In our real-world cohort study, not attaining LDAS or remission at baseline and aPL positivity was associated with higher risk of disease flares in patients with low-grade SLE