PurposeTo determine the relationships between impact of secondary health conditions (SHCs), treatment of SHCs, and life satisfaction (LS) following spinal cord injury (SCI) across 21 countries. Hypotheses were as follows: (1) Persons with SCI and fewer SHCs report higher LS and (2) Persons who receive treatment for SHCs report higher LS than those who do not receive treatment.MethodsCross-sectional survey, including 10,499 persons with traumatic or non-traumatic SCI aged 18 years or older and living in the community. To assess SHCs, 14 items adapted from the SCI-Secondary Conditions Scale were used (range 1–5). SHCs index was calculated as the mean of all 14 items. LS was assessed using a selection of 5 items from the World Health Organization Quality of Life Assessment. LS index was calculated as the mean of these 5 items.ResultsSouth Korea, Germany, and Poland exhibited the highest (2.40–2.93) and Brazil, China, and Thailand the lowest (1.79–1.90) impact of SHCs. Indexes for LS and SHCs were inversely correlated (– 0.418;p< 0.001). Mixed Model Analysis showed that the fixed effect (key predictors of the study) of SHCs index (p< 0.001) and the positive interaction between SHCs index and treatment (p= 0.002) were significant determinants of LS.ConclusionPersons with SCI across the world are more likely to perceive better LS if they experience fewer SHCs and receive treatment for SHCs, in comparison to those who do not. Prevention and treatment of SHCs following SCI should be a high priority in order to improve the lived experience and enhance LS.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11136-023-03376-3.