Classroom observation of teachers is a significant part of educational measurement; measurements of teacher practice are being used in teacher evaluation systems across the country. This research investigated whether observations made live in the classroom and from video recording of the same lessons yielded similar inferences about teaching. Using scores on the Classroom Assessment Scoring System–Secondary (CLASS-S) from 82 algebra classrooms, we explored the effect of observation mode on inferences about the level or ranking of teaching in a single lesson or in a classroom for a year. We estimated the correlation between scores from the two observation modes and tested for mode differences in the distribution of scores, the sources of variance in scores, and the reliability of scores using generalizability and decision studies for the latter comparisons. Inferences about teaching in a classroom for a year were relatively insensitive to observation mode. However, time trends in the raters’ use of the score scale were significant for two CLASS-S domains, leading to mode differences in the reliability and inferences drawn from individual lessons. Implications for different modes of classroom observation with the CLASS-S are discussed.