This in situ study evaluated the Shore A hardness and phthalate concentration of 3 tissue conditioners (Coe-Comfort, Dura Conditioner, Softone) inserted into grooves on 9 maxillary dentures. Data were collected at baseline and after 3, 7, and 14 days of denture use. All materials showed a decrease in phthalate concentration and an increase in hardness over time, but the largest changes occurred during the first 3 days; 59% to 74% of the hardness variability was explained by the phthalate concentration. Overall, Coe-Comfort was softer and had less alteration in its phthalate concentration than Dura Conditioner and Softone up to day 7.