One-size implant-abutment (OSIA) connection systems have been developed for simplicity of clinical use and for a range of implant diameters. The aim of this in vitro study was to investigate the rotational load fatigue performance of different implant diameters and abutment platforms of an OSIA connection system. Narrow, regular and wide diameter implants were tested with Regular Base (RB/WB) abutments of an OSIA system (Straumann. BLX). Wide diameter implants were also tested with Wide Base (WB) abutments. This resulted in 4 test groups (n=5): N-RB/WB (Narrow, 3.5mm, RB/WB abutment), R-RB/WB (Regular, 4.0mm, RB/WB abutment), W-RB/WB (Wide, 5.0mm, RB/WB abutment) and W-WB (Wide, 5.0mm, WB abutment). A rotational load fatigue machine applied a sinusoidally varying stress at an angle of 45o, producing an effective bending moment of 35Ncm at a frequency of 10 Hz in air at 20 oC. The number of cycles to failure was recorded. Results were evaluated using ANOVA. Failed specimens were examined with SEM to evaluate the failure mode. Pristine specimens were sectioned to examine the implant-abutment connection. All specimens in the 3 test groups with RB/WB abutments failed within the range of 558,750 cycles to 4,497,619 cycles, while the W-WB test group reached the upper limit of 5 million cycles without failure. Significant difference was found between abutment platforms (P < .001). There were no significant differences found for implant diameters (P =.857). However, with increasing implant diameter, implant fracture was less common and the location of failure was more coronal and consistently at the level of the implant platform for the abutment, and at the screw neck. For wide diameter implants, WB abutments exhibited a superior fatigue performance than RB/WB abutments, and would be preferred in situations of high mechanical risk. Increasing implant diameter, when used with RB/WB abutments, did not improve fatigue performance due to the one-size prosthetic connection, but failures were less catastrophic, and coronally located, which may be advantageous in managing failures.