Correlation between thermal history and tissue destruction is of considerable importance for successful management of BPH using minimally invasive thermal therapies such as radiofrequency or microwave probes. In order to accomplish this goal, the present in vitro study assesses the cellular viability of BPH tissue subjected to different temperature-times in an experimental matrix. Hyperplastic prostatic tissue was obtained from 8 patients after the surgical removal of the glands for other reasons (typically cancer). A piece of tissue was taken from the lateral lobe of the gland and was then sectioned into multiple thin strips (1mm thick), placed on a coverslip and heated on a thermally controlled copper block to various temperatures (45°C-70°C) for various times (1 minute–60 minutes). After heat treatment, the tissue slices were cultured for 72 hours and viability data was obtained using two independent assays: histology and dye uptake. Results indicate that the hyperplastic prostate tissue showed a progressive histologic increase in irreversible stromal tissue injury with increasing temperature-time severity. A small amount (∼5% or less) of stromal apoptosis was found in the control and mildly treated tissue. Dye uptake studies for stromal viability paralleled the histologic findings for the temperature-time combinations explored in the present study. In vitro thermal injury thresholds for 90% destruction of human BPH tissue were identified at 45°C-60min, 55°C-20min, 60°C-5min and 70°C-2 min. The Arrhenius model of injury was fit to the viability data after controlled heating to obtain parameters that will allow the prediction of injury under variable heating conditions. Arrhenius analysis of both assays showed a break point at 60°C based on 90% normalized survival. The activation energy (E) values for temperatures below and above the break point were 199.05 and 66.04 kJ/mole for the dye uptake study and 162.6 and 62.99 kJ/mole for histology. The corresponding frequency factor (A) values below and above the break point were 1.81 × 1030 and 1.82 × 109 s−1 for dye uptake study and 2.84 × 1024 and 6.64 × 108 s−1 for histology. This study is the first to report Arrhenius parameters for human BPH tissue for supraphysiological thermal therapy and will be useful for prediction of tissue destruction during thermal therapy of BPH in the clinic.