Abstract Objectives Increased work-related physical strain associates with higher subclinical joint inflammation in the rheumatoid arthritis(RA) at-risk phase of clinically suspect arthralgia and with progression to RA. Based on this, we hypothesized that work-related physical strain is also associated with the severity of joint inflammation at RA-diagnosis. We studied this in ACPA-positive and ACPA-negative RA separately, because of differences in etiopathology. Methods 197 ACPA-positive and 220 ACPA-negative consecutively diagnosed RA-patients reported occupation. Physical strain was quantified as exposure using International Standard Classification of Occupations-1988. Joint inflammation at diagnosis was measured with physical joint examination(SJC44) and with magnetic resonance imaging(MRI) of hands and forefeet (evaluating total inflammation, synovitis, tenosynovitis, osteitis, and intermetatarsal bursitis). Associations between physical strain and joint inflammation were studied using negative binomial regression, yielding incidence rate ratios(IRR). Results In ACPA-positive RA at diagnosis, increased physical strain associated with more swollen joints (IRR 1.07, 95% confidence interval(CI) 1.02-1.12). This related to more swollen hand joints (IRR 1.07, 95% CI 1.01-1.13). Increased physical strain also associated with higher joint inflammation scores on MRI (IRR 1.05, 95% CI 1.01-1.09). This was particularly driven by higher osteitis scores (IRR 1.07, 95% CI 1.01-1.13). In ACPA-negative RA at diagnosis, work-related physical strain was not associated with joint inflammation at physical examination or on MRI. Conclusions Physical strain is a risk factor for more severe joint inflammation at diagnosis in ACPA-positive, but not in ACPA-negative RA. This differential risk factor aggravating joint inflammation adds to the growing evidence of pathophysiological differences between the two RA-entities.