BACKGROUND: It is not known whether baseline prostate health index (PHI) at the initiation of active surveillance (AS) or repeated PHI testing during AS is of clinical value after confirmatory biopsy in AS men followed with multiparametric magnetic resonance imaging (mpMRI). METHODS: We identified 382 AS patients with no greater than Grade Group 1 (GG1) prostate cancer on diagnostic and confirmatory biopsy, at least one mpMRI and PHI test, of which 241 had at least 2 PHI tests. Grade reclassification (GR) was defined as ≥GG2 on surveillance biopsy. PHI risk categories 1 to 4 were as defined by the manufacturer. Associations between baseline PHI risk category or baseline PSA density (PSAD), change in PHI risk categories over time or PSAD changes over time and GR were evaluated with multivariable Cox proportional hazard regression models adjusted for age, Prostate Imaging-Reporting and Data System score and number of positive cores. RESULTS: Men with baseline PHI scores in the highest risk categories had lower rates of GR-free survival (log-rank P < 0.001), as did those who increased in PHI risk category or remained in a high PHI risk category during surveillance (log-rank P = 0.032). On multivariable regression, baseline PHI risk category was a predictor of GR (risk category 4 [vs. 1] hazard ratio [HR] 2.74, 95% confidence interval [CI] 1.32-5.66, P = 0.002, model C-index 0.764, Akaike Information Criterion [AIC] 797), as were PHI risk category changes over time (risk category 4 [vs. 1] HR 4.20, 95% CI 1.76-10.05, P = 0.002, C-index 0.759, AIC 489). Separate models with baseline PSAD and PSAD changes over time yielded C-indices of 0.709 (AIC 809) and 0.733 (AIC 495) respectively. CONCLUSIONS: Baseline PHI risk category and PHI changes over time were both independent predictors of GR after confirmatory biopsy, but the added benefit over PSAD seemed modest. However, baseline PHI and PHI risk category changes provided clinically useful risk stratification for time to GR, so further evaluation of PHI's ability to help reduce the frequency of mpMRI and/or surveillance biopsies with more PHI data points over time may be warranted.