Background <p>The association between the tumor immune microenvironment (TiME) in upper tract urothelial carcinoma (UTUC) and its prognosis remains unclear. We investigated the relationship between TiME and UTUC recurrence patterns.</p> Methods <p>We evaluated 90 patients who underwent nephroureterectomy for UTUC and divided them into nonrecurrence, distant metastasis, and intravesical recurrence-only groups. We assessed the association of the TiME with clinicopathological factors using surgical tissues and the prognosis of the three groups via multiplex fluorescence immunohistochemistry.</p> Results <p>The median age was 71&#xa0;years (44–89), and 58 (64%) were male. Intratumoral CD4⁺ T cell density was significantly higher in the nonrecurrence group (<i>p </i>= 0.0004) than the other groups, whereas intra- and peritumoral regulatory T cell (Treg; CD3⁺CD4⁺FoxP3⁺&#xa0;cell) density was higher in the distant metastases group than the intravesical recurrence-only group (<i>p</i> = 0.0025). In the multivariate analysis, pathological T stage and CD4⁺ T cells, and pathological T stage and Treg were independent predictors of recurrence-free survival (<i>p</i> = 0.045, <i>p</i> = 0.017) and metastatic-free survival (<i>p</i> = 0.027, <i>p</i> = 0.011), respectively.</p> Conclusions <p>Our study demonstrated that CD4⁺ T cells and Tregs in the TiME of patients with UTUC were independent predictors of high-risk recurrence together with high pathological stage. The analysis of TiME in surgical specimens may provide an objective indicator of the efficacy of adjuvant therapy in UTUC.</p>