The aim of this study was to investigate the influence of the cementation strategy on the fatigue resistance of zirconia crowns. The null hypothesis was that the cementation strategy would not affect the fatigue resistance of the crowns. Seventy-five simplified molar tooth crown preparations were machined in glass fiber-filled epoxy resin. Zirconia crowns were designed (thickness=0.7 mm), milled by computer-aided design/computer-aided manufacturing, and sintered, as recommended. Crowns were cemented onto the resin preparations using five cementation strategies (n=15): ZP, luting with zinc phosphate cement; PN, luting with Panavia F resin cement; AL, air particle abrasion with alumina particles (125 μm) as the crown inner surface pretreatment + Panavia F; CJ, tribochemical silica coating as crown inner surface pretreatment + Panavia F; and GL, application of a thin layer of porcelain glaze followed by etching with hydrofluoric acid and silanization as crown inner surface pretreatment + Panavia F. Resin cement was activated for 30 seconds for each surface. Specimens were tested until fracture in a stepwise stress fatigue test (10,000 cycles in each step, 600 to 1400 N, frequency of 1.4 Hz). The mode of failure was analyzed by stereomicroscopy and scanning electron microscopy. Data were analyzed by Kaplan-Meier and Mantel-Cox (log rank) tests and a pairwise comparison (p<0.05) and by Weibull analysis. The CJ group had the highest load mean value for failure (1200 N), followed by the PN (1026 N), AL (1026 N), and GL (1013 N) groups, while the ZP group had the lowest mean value (706 N). Adhesively cemented groups (CJ, AL, PN, and GL) needed a higher number of cycles for failure than the group ZP did. The groups' Weibull moduli (CJ=5.9; AL=4.4; GL=3.9; PN=3.7; ZP=2.1) were different, considering the number of cycles for failure data. The predominant mode of failure was a fracture that initiated in the cement/zirconia layer. Finite element analysis showed the different stress distribution for the two models. Adhesive cementation of zirconia crowns improves fatigue resistance.