The natural history of irritable bowel syndrome is unclear, including the likelihood that these patients will be diagnosed with an alternative organic or functional gastrointestinal disorder. Understanding the stability of an irritable bowel syndrome diagnosis may limit repeated diagnostic evaluation among these patients. The inclusion criteria included observational longitudinal studies of clinic-based samples of adult patients with irritable bowel syndrome. Only studies published in the English language in full manuscript form were included. Literature searches, selection and review of eligible articles, and data abstraction were performed in a duplicate, independent manner. Fourteen studies met study selection criteria. In six studies with relevant information, 2-5% of irritable bowel syndrome patients were diagnosed with an alternative organic GI disorder after 6 months to 6 years of follow-up. Long-term follow-up indicated that 2-18% of patients developed worse irritable bowel syndrome symptoms, approximately 30-50% of patients had unchanged symptoms, and the rest either improved or had symptoms disappear. Prior surgery (one study), higher somatic scores (one study), higher baseline anxiety (two studies), depression scores (one study) were predictive of worsening of symptoms during long-term follow-up. Irritable bowel syndrome, a chronic disorder, is a stable diagnosis. Once initial investigations are negative, fewer than 5% are diagnosed with an alternative organic GI disorder. Repeated diagnostic evaluations of patients with recurrent or persistent symptoms similar to their baseline symptoms are not warranted.