Aims : To evaluate therapeutic effect and clinical safety of combination drug therapy in children with chronic functional constipation who failed with maximal amount of single agent in maintenance phase. Methods : This study enrolled 27 children with chronic functional constipation at the Konkuk university medical center, from April 2004, through September, 2009. Clinical outcomes and adverse effects of combination drug therapy were analyzed on the basis of defecation diaries and medical records. Criteria for effective therapy were defined as follows; improvement of frequency of bowel movement (same or more than 3/week), and improvement of stool consistency, and pass hard stool same or less than 2 times per month without pain or bleeding, at least for 6 weeks. Results : Twenty-three out of 27 children were enrolled. Combination drug therapy consisted of six groups; lactulose + mineral oil (N=13), lactulose + PEG 4000 (N=4), PEG 4000 + mineral oil (N=2), PEG 4000 + lactulose (N=2), lactulose + psyllium (N=1), PEG 4000 + (lactulose and psyllium) (N=1). Twenty-two children succeeded with multiple drugs (22/23) and 1 child (1/23) failed (1 from lactulose + PEG 4000). Totally, frequency of bowel movement increased (3.58±1.27/wk with monotherapy vs. 5.31±1.10/wk with multiple drugs), and this was the most prominent with PEG 4000 + lactulose. With respect to stool consistency, in all of 17, stool consistency improved with multiple drugs and this was the most prominent in PEG 4000 + (lactulose and psyllium). Synergistic adverse effects due to multiple drug therapy were not noted clinically. Conclusion : Combination drug therapy is effective and safe in children who had failed with monotherapy in maintenance phase.