The purpose of this study was to evaluate enamel wear caused by monolithic zirconia crowns and to compare this with enamel wear caused by contralateral natural antagonists. Twenty monolithic zirconia crowns were placed in 20 patients requiring full molar crowns. For measurement of wear, impressions of both jaws were made at baseline after crown cementation and at 6-month follow-up. Mean and maximum wear of the occlusal contact areas of the crowns, of their natural antagonists and of the two contralateral natural antagonists were measured by the use of plaster replicas and 3D laser scanning methods. Wear differences were investigated by the use of two-sided paired Student's t-tests and by linear regression analysis. Mean vertical loss (maximum vertical loss in parentheses) was 10 (43) μm for the zirconia crowns, 33 (112) μm for the opposing enamel, 10 (58) μm for the contralateral teeth and 10 (46) μm for the contralateral antagonists. Both mean and maximum enamel wear were significantly different between the antagonists of the zirconia crowns and the contralateral antagonists. Gender and activity of the masseter muscle at night (bruxism) were identified as possible confounders which significantly affected wear. Under clinical conditions, monolithic zirconia crowns seem to be associated with more wear of opposed enamel than are natural teeth. With regard to wear behaviour, clinical application of monolithic zirconia crowns is justifiable because the amount of antagonistic enamel wear after 6 months is comparable with, or even lower than, that caused by other ceramic materials in previous studies.