This study evaluated the reliability and failure modes of anterior implants with internal-hexagon (IH), external-hexagon (EH), or Morse taper (MT) implant-abutment interface designs. The postulated hypothesis was that the different implant-abutment connections would result in different reliability and failure modes when subjected to step-stress accelerated life testing (SSALT) in water. Sixty-three dental implants (4 × 10 mm) were divided into three groups (n = 21 each) according to connection type: EH, IH, or MT. Commercially pure titanium abutments were screwed to the implants, and standardized maxillary central incisor metallic crowns were cemented and subjected to SSALT in water. The probability of failure versus number of cycles (95% two-sided confidence intervals) was calculated and plotted using a power-law relationship for damage accumulation. Reliability for a mission of 50,000 cycles at 150 N (90% two-sided confidence intervals) was calculated. Polarized-light and scanning electron microscopes were used for failure analyses. The beta values (confidence intervals) derived from use-level probability Weibull calculation were 3.34 (2.22 to 5.00), 1.72 (1.14 to 2.58), and 1.05 (0.60 to 1.83) for groups EH, IH, and MT, respectively, indicating that fatigue was an accelerating factor for all groups. Reliability was significantly different between groups: 99% for MT, 96% for IH, and 31% for EH. Failure modes differed; EH presented abutment screw fracture, IH showed abutment screw and implant fractures, and MT displayed abutment and abutment screw bending or fracture. The postulated hypothesis that different implant-abutment connections to support anterior single-unit replacements would result in different reliability and failure modes when subjected to SSALT was accepted.