Anti-TNF agents are widely used to treat immune-mediated disorders. Reactivation of Hepatitis B virus (HBV) is associated with immunosuppressive agents and biologics such as anti-TNF. There are limited data and differing guidelines for patients with negative hepatitis B surface antigen (HBsAg-) but positive antibody to hepatitis B core antigen (anti-HBc+) on anti-TNF with regards to outcomes and need for anti-viral prophylaxis. We examined the prevalence of HBV reactivation in a single-center retrospective cohort study of 120 HBsAg-, anti-HBc+ patients on anti-TNF, totaling 346.6 patient years. One patient (0.8%) who had a detectable VL (<20 IU) prior to starting anti-TNF had reactivation of HBV with sero-conversion to positive HBsAg. Three patients (2.5%) had undetectable HBV VL prior to anti-TNF and developed detectable VL while on anti-TNF. In conclusion, there was a low rate of HBV reactivation or development of detectable HBV DNA in HBsAg-, anti-HBc+ patients on anti-TNF.