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This study uses a national probability sample of 1,027 mathematics and science teachers to provide the first large-scale empirical comparison of effects of different characteristics of professional development on teachers’ learning. Results, based on ordinary least squares regression, indicate three core features of professional development activities that have significant, positive effects on teachers’ self-reported increases in knowledge and skills and changes in classroom practice: (a) focus on content knowledge; (b) opportunities for active learning; and (c) coherence with other learning activities. It is primarily through these core features that the following structural features significantly affect teacher learning: (a) the form of the activity (e.g., workshop vs. study group); (b) collective participation of teachers from the same school, grade, or subject; and (c) the duration of the activity.