Background: To compare the potential advantages of IMRT and 3DCRT in locoregional control and toxicity in patients with LARC. Methods: This is a retrospective analysis of a cohort of 235 consecutively treated patients with T2/T4 and N0/N1 rectal adenocarcinoma who underwent 5-FU based neoadjuvant chemo-RT between 2/2006 and 8/2012. All of them were preoperatively assessed by a surgeon. Radiation modality was correlated with clinical outcome (local and distant control) and rates of acute and late toxicity were compared for hematological, GU, GI and skin. The Chi-Squared test was used to compare the patient characteristic and radiation parameters between the two arms and univariate and multivariate Cox regression analyses were also performed. Results: 140 patients (59,6%) received IMRT, and 95 patients (40,4%) received 3DCRT to a median total dose of 5040 cGy and the median age was 64,5 years. Median follow-up time was 24 months. Rates of local recurrence were similar between IMRT group and 3DCRT group and rates of distant metastases after completion of therapy were not significantly between arms. Statistically significant differences in locoregional control and survival were not found between IMRT and 3DCRT (p = 0,56 and p = 0,24 respectively), nor in colostomy free for low-lying tumors (p = 0.44) Patients who received IMRT had a high significant reduction in all grade ≥ 3 acute toxicities versus grade ≤ 2 toxicities with respect to skin (P < 0,001), hematological (p < 0,001),urinary (P = 0,017), and GI symptoms (p = 0,0006), and late GI toxicity (p < .001) as compared to those treated with 3DCRT. The incidence of grade ≥ 3 diarrhea was 16 % among 3DCRT compared to 5 % among IMRT patients. In univariate analysis, clinical T stage, age, KPS, and adjuvant chemotherapy given were associated with better overall survival (all p < 0,05) and total radiation dose was associated with better DFS (p = 0,0065) The rates of pathological complete response were similar in the 3DCRT versus IMRT (15%) Conclusions: IMRT for rectal cancer reduces all grade ≥ 2 acute and late toxicities compared to 3DCRT, reducing treatment-related morbidity associated with chemo-radiation therapy.