Background <p>To investigate whether endometriosis is associated with the risk of incident nonalcoholic fatty liver disease (NAFLD).</p> Methods <p>Data were retrieved from Nurses’ Health Study II with participants followed up from 1995 to 2017. A total of 61,649 participants were included in this prospective cohort study. The exposure of this study was laparoscopically confirmed endometriosis. We performed Cox proportional hazard regression analyses to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) of the association between endometriosis and NAFLD.</p> Results <p>A total of 4,774 incident NAFLD cases were recorded during a 1,313,067 person-years of follow-up. In the multivariable adjusted model, laparoscopically confirmed endometriosis was positively associated with the risk of NAFLD (HR: 1.17, 95% CI: 1.07 − 1.29). The results of the mediation analyses revealed that the association was partly attributable to hysterectomy/oophorectomy (31.6% mediated, 95% CI: 18.8−47.9%), hypercholesterolemia, hypertension and infertility. Further analysis revealed that the interaction effect of age was significant for the association between endometriosis and NAFLD (<i>P</i> = 0.01).</p> Conclusions <p>Laparoscopically confirmed endometriosis was positively associated with the risk of incident NAFLD. Awareness of the potential NAFLD risk should be raised for clinicians and patients during the regular follow-up of endometriosis.</p>