Periprosthetic joint infection is a costly debilitating affliction following total joint arthroplasty. Despite a relatively low incidence rate, periprosthetic joint infection is an increasing problem due to a substantial increase in arthroplasty surgeries over time. The current treatment is replacing the primary implant with a temporary bone cement spacer that releases antibiotics over time. However, the spacer is mechanically weak with an ineffective antibiotic release. Alternatively, three-dimensional (3D)-printed reservoirs in high-strength devices have the potential to release antibiotics long term in a controlled manner. In this study, 3D-printed reservoirs were loaded with calcium sulfate embedded with gentamicin. In vitro antibiotic release is tuned by varying reservoir parameters, such as channel length, diameter, and quantity. In addition, a straightforward computational model effectively predicts antibiotic release curves to rapidly design devices with a preferred release profile. Overall, this study highlights a novel approach to potentially develop high-strength joint implants with the long-term effective release of antibiotics to treat the periprosthetic joint infection.