Introduction. Preoperative radiation regimens reduce local recurrence rates in rectal cancer. Hypofractionated radiation may improve patient compliance and lower health care costs.Aim. To analyze short term results of hypofractionated preoperative radiation for rectal cancer in a pilot study; and compare with a matched group undergoing surgery without preop radiation.Materials and Methods. Retrospective analysis of 21 consecutive, prospectively evaluated patients of rectal cancer who underwent 5x5Gy radiation from March 04 to Feb 06. The study group included patients aged 18-70 years with rectal adenocarcinoma, within 15cm from anal verge, assessed on CT scan as T3 or node positive. Exclusions were previous irradiation or malignancies, obstruction, T4 stage or metastatic lesions. Radiation was administered by a 4-port 15MV linear accelerator after CT simulation followed by surgery 2 days later. The results were compared with age and sex matched controls who had surgery without preoperative radiation in the same period. Analysis was done using the SPSS statistical packageResults. There were no statistically significant differences in age, sex, stage, location, operating time, blood loss or total hospital stay between the groups.The incidence of perineal infections in abdominoperineal resections (4/5 Vs 0/4, p=0.031); number of leaks in anterior resections (6/16 Vs 0/17, p=0.007) and the duration of ICU stay (3.57 ±2.73 Vs 1.71 ±1.10, p=0.001) were higher in the radiated group. The postoperative neutrophil counts were lower (mean 4.31x10³) in the radiated group vs 8.7x10³ in controls, p= 0.001. Nine of 21 radiated patients required perioperative granulocyte macrophage colony stimulating factor to raise the absolute neutrophil count (ANC) above 2000/mm³. Postoperatively, the median ANC tended to fall in the radiated but increased in non-radiated cases. There were 2 early deaths in the radiation group - one with severe neutropenia, unexplained lactic acidosis and hemodynamic instability (postmortem marrow examination showed hypoplasia and necrosis). The second death was associated with anastomotic leak, sepsis and neutropenia. There were no local recurrences at median follow up of 14.7 months in either group. There were 2 distant recurrences in radiated group and 3 in the non-radiated group.Conclusions and Recommendations. Neutropenia has not previously been reported as a complication of hypo-fractionated radiation for rectal cancer. In view of the high incidence of neutropenia and septic complications in our study, a large randomized trial with serial monitoring of ANC and septic complications is suggested, before 5X5 radiation is adopted widely.