Objective. To assess the association of underlying diagnosis with outcomes after revision total knee arthroplasty (TKA).Methods. For this cohort study we used prospectively collected data from the Mayo Clinic Total Joint Registry on all revision TKA patients from 1993 to 2005 with 2- or 5-year response to a validated knee questionnaire that assesses pain and function. We used logistic regression to assess the odds of moderate-severe activities of daily living (ADL) limitations and moderate-severe index knee pain 2 and 5 years after revision TKA. Odds ratios (ORs) and 95% CIs are presented.Results. The underlying diagnosis for the 2- and 5-year cohorts was loosening, wear or osteolysis in 73% and 75%; dislocation, bone or prosthesis fracture, instability or non-union in 17% and 15%; and failed prior arthroplasty with components removed or infection in 11% and 11%, respectively. In multivariable adjusted analyses that included preoperative status, compared with patients with loosening/wear/osteolysis, patients with dislocation/fracture/instability/non-union had an OR of 2.1 for moderate-severe ADL limitation (95% CI 1.3, 3.1, P < 0.001) and those with failed prior arthroplasty/infection had an OR of 1.1 (95% CI 0.6, 1.8, P = 0.4). At 5 years, differences were no longer significant. In multivariable adjusted analyses, compared with patients with loosening/wear/osteolysis, patients with dislocation/fracture/instability/non-union had an OR of 2.0 for moderate-severe pain (95% CI 1.3, 3.1, P < 0.01) at 2 years and an OR of 2.1 (95% CI 1.3, 3.8, P = 0.01) at 5 years. Failed prior arthroplasty/infection was not significantly different than the reference category.Conclusion. Underlying diagnosis is independently associated with ADL limitations and pain after revision TKA. This information can help patients have realistic expectations of outcomes. Published by Oxford University Press on behalf of the British Society for Rheumatology 2013. This work is written by US Government employees and is in the public domain in the US.