A liquid chromatography-tandem mass spectrometry method for the simultaneous detection of cotinine and caffeine in umbilical cord was fully validated. The analytes were quantified using multiple reaction monitoring and corresponding stable isotope internal standards (cotinine-d₃ and caffeine-¹³C₃). The method demonstrated acceptable imprecision (<12%) and bias (<13%). The limit of detection was 4 ng g⁻¹ and 40 ng g⁻¹ for cotinine and caffeine, respectively. The determined relative matrix effects for cotinine and caffeine were 3.0% and 3.2%, respectively. The method was used to successfully analyze two authentic umbilical cords that were matched with corresponding meconium specimens that had been analyzed for cotinine and caffeine using a previously published method. A simple, one-step collection procedure and the availability of specimen for every donor make umbilical cord a simple alternative for newborn toxicology.