Ostomy-specific adjustment may or may not predict health-related quality of life (HRQoL) and/or overall quality of life (QoL). A cross-sectional study was conducted among patients recruited from the customer registers of 8 surgical suppliers and pharmacies across Norway between November 2010 and March 2011 to determine which of the 34 items of the Ostomy Adjustment Scale (OAS) are the strongest predictors for HRQoL and overall QoL and to determine the HRQoL and overall QoL of individuals with an ostomy compared to a control group representing the general population. Persons who were >18 years old; had a permanent colostomy, ileostomy, or urostomy for >3 months; and could read and write Norwegian were invited to participate. The participants received information about the study in a letter from the researcher and returned their demographic information (addressing gender, age, marital status, education, diagnosis, time since surgery, and ostomy type) and study questionnaires using prepaid envelopes. The 158 participants (mean age 64 years [range 29-91], 89 [56%] men and 69 [44%] women) completed and returned by mail a sociodemographic questionnaire, the 34-item OAS (questions scored on a scale of 1 to 6, totally disagree to totally agree, score range 34 to 204), the Short Form-36 (SF-36, including 2 main components [physical and mental issues] divided into 8 subscales, scored from 0 to 100), and the 16-item Quality of Life Scale (QOLS) instrument (each response scored 1 to 7, from very dissatisfied to very satisfied; total score ranging from 16 to 112). Statistical analysis, including ordinary least square regression analyses, assessed whether the OAS independently predicted the sum scores of the SF-36 (physical component summary [PCS] and mental component summary [MCS]) and the QOLS score after adjusting for age, gender, marital status, education, diagnosis, time since surgery, and ostomy type. The OAS significantly predicted the SF-36 (PCS and MCS) and QOLS scores (P <0.001). Five (5) OAS items ("living a fulfilling life," "being free to travel where I want despite my ostomy," "realizing that this ostomy will be there forever," "worries about being left alone," and "embarrassing accidents in sexual activities") strongly predicted the composite score of the SF-36 (PCS and MCS) and QOLS measurements. The SF-36 scores in physical role functioning, general health, vitality, and MCS were lower in ostomy patients than controls (P < 0.05), whereas no difference was found for QOLS. Overall, ostomy-specific adjustment may be an important predictor of HRQoL and overall QoL, with the OAS factors described above having greater influence. More research such as prospective cohort studies are needed regarding patient adjustment to an ostomy.