Introduction Structural allografts and PEEK cages are commonly used as interbody fusion devices in ACDF. The subsidence rates of these two spacers have not yet been directly compared. The primary aim of this study was to compare the subsidence rate of allograft and PEEK cage in ACDF. The secondary aim was to determine if the presence of subsidence affects the clinical outcome. Methods We reviewed 67 cases (117 levels) of ACDF with either structural allograft or PEEK cages. There were 85 levels (48 cases) with PEEK and 32 levels (19 cases) with allograft spacers. All surgeries were performed by a fellowship-trained spine surgeon from November 2005 to September 2012. Immediate postoperative and 6-month lateral cervical radiographs were evaluated for subsidence by measuring the anterior disc height and posterior disc height at each operative level. Subsidence was defined as a decrease in anterior or posterior disc heights > 1 mm. The subsidence rate between the two groups was compared using the chi-square to test for significance (α = 0.05). NDI was recorded to evaluate the clinical outcome of the subsidence (SG) and nonsubsidence groups (NSG). t-test was used to test for difference between the two groups (α = 0.05). Results There was no statistically significant difference between subsidence rate of the PEEK group (54%; 46/685) and the allograft group (59%; 19/32) ( p = 0.69). Overall mean subsidence was 1.0 ± 1.3 mm anteriorly and 1.2 ± 1.2 mm posteriorly. The mean NDI improvement was 11.7 (from 47.1 to 35.4; average follow-up: 12 months) for the SG and 14.0 (from 45.8 to 31.8; average follow-up: 13 months) for the NSG ( p = 0.74). Conclusion The subsidence rate does not seem to be affected by the use of either PEEK or allograft as spacers in ACDF. Furthermore, subsidence alone does not seem to be predictive of clinical outcomes of ACDF.