OBJECTIVES: Total knee arthroplasty (TKA), one of the most painful surgical procedures, is projected to increase almost eight-fold, from 450,000 in 2005 to 3.48 million in 2030, attributable to population aging and obesity. Accordingly, advances in pain management techniques are highly relevant to orthopedic surgery. Two common pain management methods after TKA are nerve block (NB) and periarticular injection (PAI). This study explored whether either technique provided advantages in patient outcomes and satisfaction. METHODS: This is a retrospective study comparing adult patients who received NB (N=514) versus PAI (N=483) of ropivacaine, epinephrine, ketorolac, and morphine, for primary TKA at Mayo Clinic, Florida from 2013-2016. We compared patient outcomes including: pain scores, time after surgery to first ambulation, cumulative postoperative distance walked, postoperative length of stay, and discharge disposition. Patient satisfaction with pain control was also captured, along with resource utilization measures including emergency visits, readmissions, and revisions. RESULTS: Our results indicated that PAI was associated with lower pain during the 24 hours after surgery (mean score, on a 0to10 scale: NB=2.4 vs. PAI=1.7;P<0.001) compared to NB, but thereafter, until discharge, there was no difference (mean: NB=3.2 vs. PAI=3.1;P=0.370). PAI was associated with earlier knee ambulation (mean: NB=31.3 vs. PAI=22.3 hours;P<0.001), longer walking distance (mean: NB=21.4 vs. PAI=50.3 meters;P<0.001), shorter hospital stay (mean: NB=2.9 vs. PAI=2.3 days;P<0.001), more discharges to home (NB=48.3% vs. PAI=79.3%;P<0.001), and better patient satisfaction with pain control (mean score, on a 0to100 scale: NB= 88.4 vs. PAI= 92.7;P=0.006) compared to NB. Resource utilization measures (emergency visits, readmissions, and revisions) were similar between the two groups (P>0.05). CONCLUSIONS: With increasing demand for TKA and based on early evidence, providers and policymakers should consider PAI as an efficient pain management approach. This method has proven to provide better patient satisfaction with pain control, earlier and further mobilization, and quicker discharges, which accordingly impacts cost.