BACKGROUND Preoperative concurrent chemoradiation therapy (CRT) with either capecitabine or 5-florouracil/leucovorin (5 FU/LV) is the standard of care in locally advanced rectal cancer (LARC). Literature comparing the toxicity and response of these two regimens in Indian patients is sparse. Our objective was to compare the pathological response (PR) and clinical outcome of capecitabine versus 5 FU/LV in CRT for LARC. METHODS Sixty patients with LARC treated with preoperative CRT with capecitabine or 5FU/LV from January 2009 to May 2014 were analyzed. Ryan's tumor regression grading was used for PR assessment and tumor downstaging was defined as a reduction in the T and N stages by at least one level. Toxicity was assessed with RTOG acute toxicity assessment criteria and CTCAE 4.0 version. Statistical analysis was done using IBM SPSS 20 software. Percentage of patients with respect to response rates and toxicities was computed in each of the treatment groups. To test the statistical significance of the difference in PR rates and toxicities between the two groups, Chi-square test was used. Kaplan-Meier estimate of survival rate was computed for each group. To test the statistical significance of the difference in survival rate, the log-rank test was applied. CONCLUSIONS The two groups (5 FU/LV vs. capecitabine) were comparable with respect to pathological complete response (20% vs. 24%), pathological downstaging (76% vs. 69%), sphincter preservation rates, and acute complication rates. Both regimens were well tolerated. Overall survival and disease-free survival also did not show a statistically significant difference between the two groups (P values 0.720 and 0.255, respectively). In summary, our analysis showed the equivalence of both regimens in the preoperative CRT setting.