We report a case of accidental nicotine intoxication following transdermal exposure in a 22-year-old man with no medical history, who worked in a company manufacturing e-liquids for electronic cigarettes. He accidentally spilled 300 mL of pure nicotine solution (>99%) on his right leg without wearing protective clothing or a mask. Less than a minute later, he experienced dizziness, nausea, and headaches, followed by painful burning sensations in the affected area. He immediately removed his pants and washed his leg thoroughly with water. He presented to the emergency department two hours later, where he exhibited a respiratory rate of 25 cpm, a heart rate of 70 bpm, headaches, abdominal pain, pallor, and vomiting. He recovered without specific treatment five hours post-intoxication. Plasma levels of nicotine, cotinine, and hydroxycotinine were measured five hours after exposure using liquid chromatography–mass spectrometry. The concentrations found were 447 ng/mL for nicotine, 1254 ng/mL for cotinine, and 197 ng/mL for hydroxycotinine. Nicotine is an alkaloid that can be highly toxic, with doses of 30–60 mg being potentially fatal. Transdermal intoxication is rare, with very few cases reported in the literature. This case highlights the risk of acute intoxication through cutaneous exposure to nicotine-containing liquid products and the need for protective clothing when handling such products in a professional context.