Objective To investigate the progression of rotator cuff tendon pathology across one year in manual wheelchair (MWC) users with spinal cord injury (SCI) and matched able-bodied individuals, and to explore the association between pain, age, and duration of wheelchair use with the progression of rotator cuff pathology. Design Longitudinal cohort study, 1-year follow-up. Setting Outpatient clinic at a tertiary medical center. Participants Twenty-four adult MWC users with SCI (20 men) with an average age (SD) of 37(12) years and 24 age and sex-matched able-bodied individuals. Interventions Not applicable. Main outcome measure(s) Presence of shoulder pain was collected. Magnetic resonance imaging (MRI) abnormalities of rotator cuff tendons including tendinopathy and tendon tears at baseline and 1-year follow-up visits were graded by a board-certified musculoskeletal radiologist, and three categories of tendon pathology scores including individual tendon scores, unilateral cuff scores, and bilateral cuff scores were calculated for each participant. Results Fifty-four percent of the MWC users reported shoulder pain at both time points which was significantly higher than able-bodied cohort at baseline (17%, P = 0.012) and year 1 (21%, P = 0.021). Rotator cuff tendon pathology was detected as mainly mild tendinopathies and low-grade partial-thickness tears in both cohorts at both time points but was more common in MWC users. The results for the bilateral cuff scores indicated a significant (P < 0.008) progression of rotator cuff tendon pathology in the MWC users over one year. MRI findings did not change significantly for the able-bodied cohort across time. There was no association of pain, age, or duration of MWC use with progression of rotator cuff pathology in MWC user cohort. Conclusion MWC users had a higher prevalence of pain than matched able-bodied cohort, but pain was minimal and not function-limiting. Bilateral cuff TOTAL scores showed pathology progression in MWC users, but MRI findings remained stable in the able-bodied cohort. MWC users were 3.4 times more likely to experience pathology progression than the able-bodied cohort.