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There has been some question about the classification of painful constipation (PC) and its relationship to irritable bowel syndrome (IBS), and in particular IBS with constipation (IBS-C). We sought to: (1) compare PC with IBS and its subtypes (IBS-C, IBS-D, and IBS-A) in terms of pain scores, stool habit and clinical features, and to determine which factors predict PC over IBS, (2) determine the variation in pain and stool habit for PC relative to IBS over time, and (3) compare whether there are clinical differences between those with high pain constipation (HPC) and low pain constipation (LPC) over time.Among 231 women in an National Institutes of Health trial, Rome II moderate to severe PC (n=41), IBS-A (n=55), IBS-C (n=80), and IBS-D (n=55) received diary cards on stool frequency, consistency, and pain (visual analog scale) daily for 14 days before and after 12-week treatment and at 3-month intervals for 1 year. PC was characterized into HPC (high pain) and LPC (low pain) groups based on visual analog scale pain scores (high pain ≥50 and low pain <50) at baseline. Descriptive statistics were calculated, and comparisons performed by χ2 for categorical and t tests for continuous variables. Regressions and repeated measures tested between group and within-group associations, respectively.(a) PC is different from IBS with: higher pain scores (P=0.002), lower education (P=0.02), greater healthcare use and surgeries (P=0.05 to 0.003), and poorer daily function (Sickness Impact Profile overall P=0.004), (b) PC is similar to IBS-C and IBS-A but different from IBS-D for stool frequency and consistency (P<0.0001), bloating (P=0.02), laxative/antidiarrheal use (P=0.04 and 0.02), and lower education (P=0.02). (c) Over 1 year, PC: maintained higher pain scores than IBS, had stool frequencies less than IBS-D and between IBS-C and IBS-A, had stool consistency less than IBS-D and similar to IBS-A, (d) for HPC and LPC there was no difference in constipation, and HPC switched to LPC over time, while LPC pain scores stayed low. Limitations include the absence of a painless constipation group, and that studying moderate to severe symptoms, which may not represent all with PC or IBS.PC is clinically similar in stool pattern and bloating to IBS-C and IBS-A, but with greater pain, healthcare utilization, and poorer daily function. The findings also suggest that PC defines a population where there is greater pain, and poorer health status and daily function, which may be driven more by visceral and/or central pain dysregulation more than the constipation.