Trans-fatty acids (TFAs) are categorized into industrial TFAs (iTFAs) and ruminant TFAs (rTFAs). TFAs intakes over 48 mg/kg have been strongly associated with high risk of atherosclerosis and cardiovascular disease. However, some rTFAs have not been conclusively associated with coronary disease. Moreover, some health benefits have been suggested for rTFAs. Here, with the goal of contrasting the effects of iTFAs with rTFAs, we fed adult mice for 45 days with 168 mg/kg of trans-elaidic acid (TEA, an iTFA) or trans-vaccenic acid (TVA, an rTFA), and evaluated their serum lipid profile and their performance in an appetitive memory task. We found marked differential effects, while TEA showed strong atherogenic effects (p < 0.0001 for cholesterol, triglycerides, VLDL, LDL, and HDL versus control), TVA showed significant opposite effects than TEA (p < 0.0001 for cholesterol, triglycerides, LDL, and HDL; p = 0.0039 for VLDL). Furthermore, when these mice were trained to find a piece of feed in a slightly intricate eight-arm maze, TEA showed impairing effects on appetitive memory. Although TEA intake did not block appetitive memory, there was a clear delay in learning (p = 0.0353 versus control). Notably, TVA improved the learning performance of mice (p < 0.0001 versus control). Moreover, oleic acid, a cis isomer, showed similar effects than TVA in the appetitive learning task (p = 0.0004). Our results add to the hypothesis that intake of iTFAs have adverse effects whereas naturally occurring rTFAs could have some beneficial effects.