Background: To compare the areas of residual disease after neoadjuvant pelvic radiation with 5-FU based chemotherapy for rectal cancer using Intensity Modulated Radiation Therapy (IMRT) with simultaneous integrated boost (SIB) technique compared to 3D Conformal Radiation Therapy (3DCRT) Methods: Fourty nine (49) consecutive rectal cancer patients treated with pelvic radiation and concurrent 5-FU based chemotherapy were analyzed. We compared twenty-eight (28) patients treated on an institutional IMRT protocol versus twenty-one (21) patients treated with 3DCRT. All patients received 45-50.4 Gy to the pelvis in 3DCRT group. All patients with IMRT received 45 Gy in 25 fractions to the pelvic no des. The primary rectal tumor recieved a simultaneous integrated boost to a dose of 50 Gy in 25 fractions. IMRT planning was done with dose constraints for bladder, rectum, and small bowel and bone marrow. All patients in both groups received 5-FU based chemotherapy during radiation. Evaluation of toxicity was based on RTOG criteria. 2 patients in the 3DCRT group and 2 in IMRT group received either growth factors or blood-products transfusion and needed hospitalization during treatment secondary to acute toxicities. Results: All patients completed their prescribed course of radiation. CR rates were 5/21(23%) in 3DCRT and 4/28(25%) in the IMRT-SIB (p-value 0.74). 9/21(42%) in 3D and 19/29(65%) in the IMRT group underwent Low anterior resection according to the location of the tumor. There was no grade 4 toxicity in the IMRT-SIB group. Overall grade 2 toxicity in 3D Vs IMRT-SIB group was - GI -52% Vs 19%, GU- 8% Vs 8%, skin 42 Vs 4%, hematologic 33 Vs 47%. Overall Grade 1 toxicity in 3DCRT Vs IMRT group was- GI- 33% Vs 52%, GU 23% vs 28%, Skin 52% Vs 38%, hematologic 4% Vs 33%. Conclusions: Neoadjuvant pelvic radiation with 5 FU for rectal cancer has similar local control rates. There is less GI, skin and hematologic toxicity when delivered via IMRT-SIB versus 3DCRT. IMRT is safe and may allow dose escalation with potential probability of increased tumor response.