© 2019 Elsevier Inc. Cognitive dysfunction is a common comorbidity in adults with treatment-resistant epilepsy (TRE). Recently, cannabidiol (CBD) has demonstrated efficacy in epilepsy treatment. However, our understanding of CBD's cognitive effects in epilepsy is limited. We examined long-term cognitive effects of CBD in adults with TRE as part of an ongoing prospective, open-label safety study. Twenty-seven adults with TRE (mean age: 34[standard deviation (SD) + 14], female 52%) enrolled in the UAB CBD program completed standardized cognitive testing (NIH Toolbox Cognition Battery (NIHTB-CB)) at pre-CBD administration baseline and at one-year follow-up. Participants were receiving stable CBD dose at the time of one-year testing (mean = 36.5 mg/kg/day). The NIHTB-CB consisted of two global composite scales (Fluid and Crystallized) and seven individual tests measuring aspects of working memory, episodic memory, executive function, processing speed, and language. All participants had recorded Chalfont Seizure Severity Scale (CSSS) scores at each visit. Statistical analyses included t-test, Pearson correlation coefficient, and multivariate one-way ANOVA. At baseline, cognitive test performance was below average for both global composite scales (Fluid: 71 [± 18] range: 46–117) and Crystallized (76 [± 15] range: 59–112)]. Longitudinal analysis revealed no significant group change across the two global composite scales. Of the seven individual cognitive tests, none changed significantly over time. No correlation was found between the cognitive change scores and CBD dose (all P's ≥; 0.2). Change in cognitive test performance was not associated change in seizure severity rating. These findings are encouraging and indicate that long-term administration of pharmaceutical grade CBD is overall cognitively well-tolerated in adults with TRE.