<h3>Objective:</h3> To examine the predictors of time to premature gonadal failure (PGF) in patients with systemic lupus erythematosus from LUMINA, a multiethnic US cohort. <h3>Methods:</h3> PGF was defined according to the SLICC Damage Index (SDI). Factors associated with time to PGF occurrence were examined by univariable and multivariable Cox proportional hazards regression analyses: three models according to cyclophosphamide use, at T0 (model 1), over time (model 2) and the total number of intravenous pulses (model 3). <h3>Results:</h3> Thirty-seven of 316 women (11.7%) developed PGF (19 Texan–Hispanics, 14 African–Americans, four Caucasians and no Puerto Rican–Hispanics). By multivariable analyses, older age at T0 (hazards ratio (HR) = 1.10–1.14; 95% CI 1.02–1.05 to 1.19–1.23) and disease activity (Systemic Lupus Activity Measure-Revised) in all models (HR = 1.22–1.24; 95% CI 1.10–1.12 to 1.35–1.37), Texan–Hispanic ethnicity in models 2 and 3 (HR = 4.06–5.07; 95% CI 1.03–1.25 to 15.94–20.47) and cyclophosphamide use in models 1 and 3 (1–6 pulses) (HR = 4.01–4.65; 95% CI 1.55–1.68 to 9.56–13.94) were predictors of a shorter time to PGF. <h3>Conclusions:</h3> Disease activity and Texan–Hispanic ethnicity emerged as predictors of a shorter time to PGF while the associations with cyclophosphamide use and older age were confirmed. Furthermore, cyclophosphamide induction therapy emerged as an important determinant of PGF.