Many individuals who undergo total knee replacement (TKR) become long-term opioid users after TKR. Associations of physical therapy (PT) interventions before or after TKR with long-term use of opioids are not known. To evaluate associations of PT interventions before and after TKR with long-term opioid use after TKR. This cohort study used data from the OptumLabs Data Warehouse on 67 322 individuals aged 40 years or older who underwent TKR from January 1, 2001, to December 31, 2016, stratified by history of opioid use. The analyses for the study included data from January 1, 1999, to December 31, 2018. Any PT interventions within 90 days before or after TKR, post-TKR PT dose as number of sessions (ie, 1-5, 6-12, and ≥13 sessions), post-TKR PT timing as number of days to initiation of care (ie, <30 days, 31-60 days, or 61-90 days after TKR), and post-TKR PT type (ie, active vs passive). The association of pre- and post-TKR PT with risk of long-term opioid use occurring more than 90 days after TKR was assessed using logistic regression while adjusting for confounders, including age, sex, race and ethnicity (Asian, Black, Hispanic, or White), obesity, type of insurance, geographical location, and physical and mental health comorbidities. A total of 38 408 opioid-naive individuals (21 336 women [55.6%]; mean [SD] age, 66.2 [9.2] years) and 28 914 opioid-experienced individuals (18 426 women [63.7%]; mean [SD] age, 64.4 [9.3] years) were included. Receipt of any PT before TKR was associated with lower odds of long-term opioid use in the opioid-naive (adjusted odds ratio [aOR], 0.75 [95% CI, 0.60-0.95]) and opioid-experienced (aOR, 0.75 [95% CI, 0.70-0.80]) cohorts. Receipt of any post-TKR PT was associated with lower odds of long-term use of opioids in the opioid-experienced cohort (aOR, 0.75 [95% CI, 0.70-0.79]). Compared with 1 to 5 sessions of PT after TKR, 6 to 12 sessions (aOR, 0.82 [95% CI, 0.75-0.90]) and 13 or more sessions (aOR, 0.71 [95% CI, 0.65-0.77) were associated with lower odds in the opioid-experienced cohort. Compared with initiation of PT within 30 days after TKR, initiation 31 to 60 days or 61 to 90 days after TKR were associated with greater odds in the opioid-naive (31-60 days: aOR, 1.45 [95% CI, 1.19-1.77]; 61-90 days: aOR, 2.15 [95% CI, 1.43-3.22]) and opioid-experienced (31-60 days: aOR, 1.10 [95% CI, 1.02-1.18]; 61-90 days: aOR, 1.32 [95% CI, 1.12-1.55]) cohorts. Compared with passive PT, active PT was not associated with long-term opioid use in the opioid-naive (aOR, 1.00 [95% CI, 0.81-1.24]) or opioid-experienced (aOR, 0.99 [95% CI, 0.92-1.07]) cohorts. This cohort study suggests that receipt of PT intervention before and after TKR, receipt of 6 or more sessions of PT care after TKR, and initiation of PT care within 30 days after TKR were associated with lower odds of long-term opioid use. These findings suggest that PT may help reduce the risk of long-term opioid use after TKR.