Most orthographic coding models are based on the assumption that the orthographic code does not distinguish between vowels and consonants and, therefore, those models predict no difference between vowel (cisano-CASINO) and consonant (caniso-CASINO) transposed-letter (TL) effects. The available data, however, do provide some evidence for a consonant–vowel distinction at the level of the orthographic code. Most centrally, masked priming lexical decision tasks, mainly carried out in Spanish, have shown priming from consonant TL primes (e.g., caniso) but not from vowel TL primes (e.g., cisano). The present experiments were an investigation of this pattern. Experiment 1, based on Schubert, Kinoshita, and Norris’ (2018) stimuli which showed no consonant–vowel differences in an unprimed same-different task, also showed no consonant–vowel differences in masked TL priming effects in lexical decision showing, for the first time, a vowel TL priming effect in that task. Experiment 2, using Lupker, Perea, and Davis’ (2008) Experiment 1a stimuli, also showed a small but significant vowel TL priming effect (a nonreplication of that experiment), while replicating the consonant TL priming effect that those authors originally reported. In Experiment 3, TL priming was again essentially unaffected by the consonant-vowel status of the letters involved as well as by target frequency, a variable on which the Experiment 1 and 2 stimuli differed. These results, supported by evoked response potential (ERP) results from other labs, suggest that consonant–vowel TL differences, when they do emerge in English, are likely are not due to the nature of the orthographic code.