Since their introduction to the market in 2007, electronic cigarettes (e-cigarettes) have become increasingly popular. Alarmingly, these products allow for easy consumption of drugs such as nicotine and cannabis, either alone or in combination. Unfortunately, nicotine and cannabis are the most commonly used drugs among pregnant women and both may place the fetus at a higher risk for developing cognitive impairments. While there is no known treatment for the effects of prenatal drug exposure, clinical evidence suggests that maternal levels of the essential nutrient choline are associated with reduced risk to adverse effects of marijuana on the developing fetus. Thus, the present study investigated the ability of early choline supplementation to mitigate the effects of prenatal exposure to nicotine, THC, and the combination of both via e-cigarette on spatial learning and memory. Pregnant Sprague-Dawley dams were placed in a vapor inhalation chamber from gestational days (GD) 5-20. Subjects were exposed to either THC (100 mg/mL), nicotine (36 mg/mL), the combination of both, or propylene glycol (vehicle control), via e-cigarette (6-sec puff every 5 min for 30 minutes per day). From postnatal days (PD) 10-30, male and female offspring received subcutaneous injections of either choline chloride (100 mg/kg) or saline. Subjects were tested on a Morris Water Maze spatial learning and memory task from PD 40-46, in which subjects had to locate an escape platform in a pool of water using visuospatial cues. During acquisition, subjects exposed to THC only were less thigmotaxic, suggesting that they were less anxious. In addition, females exposed to THC were less accurate in their swim direction and took longer path lengths, indicating spatial memory deficits, an effect attenuated with choline. During the probe trial, choline supplementation improved spatial memory among females exposed to THC, alone or in combination with nicotine. These findings suggest that choline can improve spatial learning and memory in subjects exposed to prenatal THC. These data suggest that postnatal nutrition may modify cognitive performance in subjects exposed to prenatal cannabis in a sex-dependent manner. Supported by TRDRP 28IP-0026 and 5R37AA012446.