Prior studies found conflicting results about whether lupus is likely to flare during or after pregnancy. Using a large cohort of pregnant and non-pregnant women with lupus, we estimated the effect of pregnancy on disease flares in systemic lupus erythematosus. Data were collected in the Hopkins Lupus Cohort 1987-2015. Women aged 14-45 years with >1 measurement of disease activity were included. The time-varying exposures were classified as pregnancy, postpartum or non-pregnant/non-postpartum periods. Flares were defined as: (1) change in Physician Global Assessment (PGA)≥1 from previous visit and (2) change in Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI)≥4 from previous visit. A stratified Cox model estimated HRs with bootstrap 95% CIs. There were 1349 patients, including 398 pregnancies in 304 patients. There was an increased rate of flare defined by PGA during pregnancy (HR: 1.59; 95% CI 1.27 to 1.96); however, this effect was modified by hydroxychloroquine (HCQ) use, with the HR of flares in pregnancy compared with non-pregnant/non-postpartum periods estimated to be 1.83 (95% CI 1.34 to 2.45) for patients with no HCQ use and 1.26 (95% CI 0.88 to 1.69) for patients with HCQ use. The risk of flare was similarly elevated among non-HCQ users in the 3 months postpartum, but not for women taking HCQ after delivery. Our study supports and extends previous findings that the incidence of flare is increased during pregnancy and within the 3 months postpartum. Continuing HCQ, however, appeared to mitigate the risk of flare during and after pregnancy.