The purpose of this efficacy study was to examine the impact of the Teacher Study Group (TSG) professional development program in vocabulary, on teacher knowledge, observed teaching practice, and student vocabulary achievement, when implemented with first grade teachers in Title 1 schools. This multi-site cluster randomized trial was implemented in 61 schools from 16 districts in four states (California, Texas, Ohio, and Illinois). The analytic sample included 182 first grade teachers and 1,680 of their students. Significant impacts were found at the teacher level for teacher knowledge (g = 0.38, p < 0.05), the "Teacher-Directed Vocabulary Instruction" scale (g = 0.93, p < 0.001), and the "Interactive Vocabulary Instruction" scale (g = 0.47, p < 0.05). No significant impacts were found at the student level on the "Woodcock-Johnson Oral Vocabulary" and "Reading Vocabulary" subtests and the "GRADE Word Meaning" subtest.