BACKGROUND: Laboratory tests are obtained following total joint arthroplasty (TJA) despite a lack of supporting evidence. No prior study has prospectively analyzed the effect of discontinuing routine laboratory tests. This study aimed to determine whether discontinuing routine laboratory tests in TJA patients resulted in a difference in 90-day complications. METHODS: This was a prospective protocol change study at a high-volume center. Prior to protocol change, patients underwent routine laboratory tests following primary unilateral TJA (control group). After the change, an algorithmic approach was used to selectively order laboratory tests (protocol group). Patients with bleeding disorders, chronic obstructive pulmonary disease, arrhythmia, coronary artery disease, congestive heart failure, chronic renal failure, dementia, abnormal preoperative sodium, potassium, or hemoglobin <10 g/dL were excluded. In-hospital and 90-day data were collected. Student's t-test was used to analyze continuous variables and chi-squared test was used for categorical variables. A pre-hoc analysis examining the primary outcome required 607 patients per group to achieve 80% power. RESULTS: The protocol group included 937 patients, whereas the control group included 891 patients. The protocol group had fewer females and total hip arthroplasties. There were no differences in age, body mass index, American Society of Anesthesiologists classification, tranexamic acid administration, or estimated blood loss between the protocol and control groups. There were also no differences in transfusions, electrolyte corrections, unplanned consults, length of stay, or transfers. The protocol cohort had more fluid boluses and home discharges. There was no difference in 90-day complications between the 2 groups. CONCLUSIONS: This study utilizing an algorithmic approach to laboratory collection demonstrates that discontinuing routine laboratory tests following TJA is safe and effective. We believe this protocol can be implemented for most patients undergoing primary unilateral TJA.