Objectives Prospective practice‐based clinical evaluation of chairside fabricated monolithic partial crowns composed of zirconia‐containing lithium silicate (ZLS) ceramic material. Materials and Methods Between October 2013 and September 2014, 71 patients were restored with 92 partial crowns on vital or sufficiently endodontically treated teeth. The monolithic restorations were fabricated chairside (Cerec SW 4.2/Cerec MC XL) from a glaze‐fired ZLS ceramic material (Celtra Duo, Dentsply Sirona, Bensheim, Germany). Adhesive cementation was performed using the total‐etch technique with one of two dual‐curing composite materials. Modified United States Public Health Service parameters were evaluated annually; moreover, the parameters “time‐dependent survival” (in situ criterion) and “success rates” (event‐free restorations) were evaluated according to Kaplan‐Meier analysis. Results Sixty‐nine patients with 17 premolar and 71 molar partial crowns attended annual follow‐up examinations (observational period: 36.0 ± 5.7 months). Two complete failures were recorded and were caused by a tooth fracture (at 30 months) and a restoration fracture (at 38 months), (3‐year survival rate: 99%; 95% confidence interval (CI 95%): [0.97;1]). One clinical intervention was necessary (endodontic treatment) to maintain function (3‐year success rate: 98%; (CI95%: [0.95:1]). Conclusions Chairside‐fabricated ZLS partial crowns show a good initial clinical performance. However, to further evaluate this new material, clinical data from studies with longer observational periods are required. Clinical Significance Based on this mid‐term evaluation, ZLS ceramics appear to be a promising alternative material for the chairside fabrication of adhesively luted monolithic posterior restorations with a low risk of material‐related complications.