The objective of this study was to examine the effect of divergent selection for feed efficiency using residual feed intake (RFI) as a model on nutrient digestibility, bacterial populations, enzyme gene expression and volatile fatty acid (VFA) production. Male pigs (n = 75; initial BW 22.4 kg were fed a standard finishing diet (9.21 g/kg of standard ileal digestible lysine and 14 MJ/kg digestible energy) for 43 d before slaughter to evaluate feed intake and growth for the purpose of calculating RFI. Phenotypic RFI was calculated as the residuals from a regression model regressing average daily feed intake (ADFI) on average daily gain (ADG) and mid-test metabolic BW0.75 (MWT). Data were analyzed using the GLM procedure of SAS. Sixteen pigs (85 kg, SEM 2.84 kg), designated as high RFI (HRFI; n = 8) and 8 low RFI (LRFI) were killed and digesta was collected from the cecum and colon to determine microbial populations and VFAs. Digesta was collected from the ileum and rectum to measure coefficient of apparent ileal (CAID) and total-tract nutrient digestibility (CATTD). Mucosal scrapings from the duodenum, jejunum and ileum were used for RNA extraction and subsequent analysis of mRNA expression of several enzymes using RT-PCR. As expected LRFI pigs had lower ADFI (2.44kg vs. 1.87kg, + 0.07) and improved feed conversion ratio (1.96 vs. 2.48, SEM 0.02) than HRFI pigs (P < 0.001) with no difference in ADG or MWT. The LRFI pigs had improved CAID of GE (P < 0.05). Similarly, LRFI pigs had improved CATTD of GE, while also having improved CATTD of nitrogen and dry matter (P < 0.05). In the jejunum RFI was correlated (r = −0.46; P < 0.10) with the gene expression of the enzyme sucrase-isomaltase which is located in the intestinal brush border cells. In the colon HRFI pigs had increased concentration of acetic acid (P < 0.05). In the cecum LRFI pigs had increased molar proportions of butyric acid (P < 0.10). LRFI pigs had increased cecal lactobacillus (P < 0.05) compared with HRFI pigs. In conclusion differences in GE digestibility, sucrase-isomaltase gene expression, and populations of lactobacillus may contribute to differences in feed efficiency between RFI groups.