BACKGROUND: Quality of life (QoL) is commonly assessed in inflammatory bowel disease (IBD); the relationship of QoL within IBD states and relative to others has not been comprehensively evaluated. This systematic review, published across 2 papers, evaluates 5 key QoL comparisons. Part I, presented here, examines between-disease comparisons: (1) IBD/healthy(general) population and (2) IBD/other medically ill groups. Part II examines within-disease comparisons: (3) active/inactive disease, (4) ulcerative colitis/Crohn's disease, and (5) change over time. Outcomes using generic vs IBD-specific QoL measures were also examined. METHODS: Adult and pediatric studies were identified through systematic searches of 7 databases from the 1940s (where available) to October 2015. RESULTS: Of 6173 abstracts identified, 466 were selected for final review based on controlled design and validated measurement; 30 unique studies (23 adult, 7 pediatric) addressed the between-disease comparisons. The pooled mean QoL scores were (1) lower in adult and pediatric IBD samples compared with healthy controls (n = 19), and for both mental and physical QoL, where measured; and (2) higher but not significant for those with IBD compared with various medically ill controls (n = 15). Findings were consistent across IBD-specific and generic QoL measures. Study quality was generally low to moderate. The most common measures of QoL were the disease-specific Inflammatory Bowel Disease Questionnaire and generic SF-36 (adults), and the generic PedsQL (children). CONCLUSIONS: There was robust confirmation that QoL for individuals with IBD was poorer than for healthy individuals, for both adults and children. QoL in IBD may be better relative to some other gastrointestinal (GI) and non-GI medical conditions for children.