ICU survivors have lower quality of life (QoL) compared to a non-ICU-treated population. The reason for this is not fully understood, but differences in baseline characteristics may be an important factor. This study evaluates the roles of comorbidity and educational level as possible explanatory factors for differences in QoL in ICU survivors compared to a non-ICU-treated population. Using a provisional questionnaire with 218 questions in 13 domains on QoL after intensive care, we compared the responses from 395 adult ICU survivors and 195 non-ICU-treated controls. An initial bivariable linear correlation analysis compared the responses from the two groups. Two secondary multivariable regression analyses tested for effect modification by comorbidity and educational level, respectively, on the effect on QoL from belonging to the ICU survivor group compared to the control group. There was a significant difference in QoL between the two groups in 170 of 218 (78%) questions. In the multivariable analyses, associations between group belonging and QoL remained in 139 questions. In 59 of these, both belonging to the ICU survivor group and comorbidity was associated to QoL, in parallel to each other. Comorbidity moderated the association between group belonging and QoL in six questions, with the highest proportion of questions within the domains of cognition and urinary functions, and the lowest proportion within appetite and alcohol, physical health, and fatigue. In 26 questions, both belonging to the ICU survivor group and educational level were associated to QoL, in parallel to each other. Educational level moderated the association between group belonging and QoL in 34 questions, with the highest proportion of questions within the domains of urinary functions, ADL and physical health, and the lowest proportion within the domains of cognition, appetite and alcohol, pain, sensory functions, and fatigue. Lower QoL seen in ICU survivors compared to non-ICU-treated controls, as measured by our provisional questionnaire, cannot be explained only by a higher burden of comorbidity, and rarely by only educational level. In issues where comorbidity or educational level was associated to QoL, it often was so in parallel to an association from belonging to the ICU survivor group. Comparing QoL in ICU survivors to that of a non-ICU-treated population may be adequate despite differences in baseline characteristics.