Background/Objectives: Spinal fusion surgery is an accepted form of management for select patients who suffer from degenerative lumbar disease. The need for cost-effective durable techniques is paramount as our population ages. This study compares the radiographic and clinical outcomes of PEEK and 3D-printed titanium interbody cages. Methods: This study compared two cohorts which underwent either PEEK or 3D-printed titanium (3DPT) interbody fusion at a single institution between 2013 and 2022. The PEEK cohort was a retrospective analysis of a prospectively collected registry. The 3DPT data were prospectively collected. The inclusion criteria were adults >18 years who underwent 1 or 2 level lumbar interbody fusion for degenerative spine disease with at least 6 months follow-up. Patient demographics, radiographs, and PROMs were collected. The cohorts were compared using ANOVA for continuous variables and Fisher’s exact test for categorical variables, with significance set to 0.05. Results: The final study included 91 patients, 49 PEEK and 42 3DPT. The 3DPT patients were older (p = 0.047) with increased incidence of hypertension (p < 0.001). The 3DPT patients had less bone morphogenetic protein (BMP) usage (80.9% vs. 54.8%; p = 0.012), but more cellular allograft (p < 0.001). Fusion rate was high for both cohorts, with PEEK at 95.9% and 3DPT at 97.6%. There was no significant difference in reoperation rate. Both the PEEK and 3DPT cohorts demonstrated an improvement in the Oswestry Disability Index (ODI) and EuroQol 5 Dimension (EQ-5D) at 1 and 2 years compared to preoperative baseline. More patients in the 3DPT group met the MCID for EQ-5D at 1 and 2 years compared to PEEK; however, this was not significant (p = 0.350; p = 1.000). Conclusions: The 3DPT interbody provided comparable if not superior fusion properties to the PEEK interbody given the decreased use of BMP. Both cohorts demonstrated similar improvements in ODI and EQ-5D compared to preoperative baseline. These results suggest that 3DPT cages may be a cost-effective alternative in spinal fusion. Further studies utilizing a larger population with higher follow-up rates are indicated to determine the economic and clinical benefits of 3DPT compared to PEEK cages in lumbar fusion surgery.