Objectives: The high rate of cannabis (CAN) use in emerging adults is concerning given prior research suggesting neurocognitive deficits associated with CAN use in youth. Regular CAN use downregulates endocannabinoid activity, while aerobic exercise upregulates cannabinoid receptor 1 activity and releases endocannabinoids. Here we investigate the influence of regular CAN use on neuropsychological performance, and whether aerobic fitness moderates these effects. Methods: Seventy-nine young adults (37 CAN users) aged 16–26 participated. Groups were balanced for aerobic fitness level. Exclusion criteria included: left-handedness, past-year independent Axis-I disorders, major medical/neurologic disorders, prenatal issues, or prenatal alcohol/illicit drug exposure. After 3 weeks of abstinence, participants completed a neuropsychological battery and a maximal oxygen consumption test (VO2 max). Multiple regressions tested whether past-year CAN use, VO2 max, and CAN*VO2 max interaction predicted neuropsychological performance, controlling for past-year alcohol use, cotinine, gender, and depression symptoms. Results: Increased CAN use was associated with decreased performance on working memory and psychomotor tasks. High aerobic fitness level was related to better performance on visual memory, verbal fluency, and sequencing ability. CAN*VO2 max predicted performance of psychomotor speed, visual memory, and sequencing ability. Conclusions: Following monitored abstinence, increased CAN use was associated with poorer performance in working memory and psychomotor speed. Higher aerobic fitness level moderated the impact of CAN on visual memory, executive function and psychomotor speed, as more aerobically fit CAN users demonstrated better performance relative to low-fit users. Therefore, aerobic fitness may present an affordable and efficacious method to improve cognitive functioning in CAN users. (JINS, 2019, 25, 134–145)