Previous research has demonstrated that infants under 17 months have difficulty learning novel words in the laboratory when the words differ by only one consonant sound, irrespective of the magnitude of that difference. The current study explored whether 15-month-old infants can learn novel words that differ in only one vowel sound. The rich acoustic/phonetic properties of vowels allow for a detailed analysis of the contribution of acoustic/phonetic cues to infants’ performance with similar-sounding words. Infants succeeded with the vowel pair /i/–/I/, but failed with vowel pairs /i/–/u/ and /I/–/u/. These results suggest that infants initially use the most salient acoustic cues for vowels and that this staged use of acoustic cues both predicts and explains why infants can learn some words that differ in only a single vowel.