OBJECTIVE Radiofrequency ablation of hepatic tumors can lead to thermal injury of surrounding structures. Both saline and 5% dextrose in water (D5) have been used to displace these surrounding structures before radiofrequency ablation. The purpose of this study was to determine the relative effectiveness of these two fluids for protecting the diaphragm and lung during radiofrequency ablation. METHODS Ten female domestic swine (mean weight, 45 kg) underwent radiofrequency ablation at open surgery. Group 1 (n = 12 lesions) was pretreated with peritoneal D5 before radiofrequency ablation. Group 2 (n = 11 lesions) was pretreated with peritoneal 0.9% saline. A 2.7-mm spacer was placed between the liver surface and diaphragm in groups 1 and 2. Group 3 (n = seven lesions) served as a control group with no pretreatment regimen. Group 4, an additional control group (n = eight lesions), consisted of animals pretreated with D5 in which a larger spacer was used. After radiofrequency ablation, the animals were sacrificed and the liver, diaphragm, and lung were removed. The extent of thermal injury to the surface of each organ was recorded. RESULTS The animals in the D5 and saline pretreatment groups experienced fewer diaphragm injuries than the control animals (D5, p = 0.02). The smallest lesions in the lung and diaphragm were in the D5 group, followed by the saline and control groups (diaphragm, p = 0.0001; lung, p = 0.13). Diaphragm lesions were significantly smaller in the D5 and saline groups than in the control group (p = 0.0001 and 0.01, respectively). CONCLUSIONS Instillation of D5 into the peritoneal cavity before hepatic radiofrequency ablation decreases the risk and severity of diaphragm and lung injuries compared with no pretreatment or pretreatment with 0.9% saline in this animal model. Pretreatment with D5 may increase both the safety of and the number of patients eligible for treatment with thermal therapies.