Literature is replete with the studies focusing on the role of vocabulary knowledge in second language receptive skills. However, the relationship between the aspects of vocabulary knowledge and productive skills in general, and the speaking performance in particular has remained scanty in the related literature. This paper examined the relationship between knowledge of L2 vocabulary size at different word-frequency levels and Iranian university students’ English-speaking ability. Moreover, the strength of this association was investigated for the fluency and lexical components of speaking ability. To achieve this goal, 46 (14 males and 32 females) Iranian English as a Foreign Language (EFL) learners, studying English Literature at Golestan University, Iran, took the Vocabulary Levels Test (VLT), a measure of size of vocabulary knowledge, and International English Language Testing System (IELTS) tasks for the speaking skill. Results of hierarchical multiple regression analyses revealed that while knowledge of the 3,000-word-frequency level (high-frequency vocabulary) contributed uniquely to the prediction of the second language (L2) overall speaking ability and its fluency dimension, knowledge of the 5,000-word frequency band (mid-frequency vocabulary) could explain the variance in the lexical dimension scores of L2 speaking over and above the high-frequency vocabulary. The implications of this study pertain to the importance of highlighting the most frequent vocabulary for academic speaking courses while attending to the lower-frequency lexical items for just the vocabulary dimension of this skill, especially for candidates taking the IELTS exam.