Total joint arthroplasty (TJA) benefit patients with osteoarthritis (OA) and rheumatoid arthritis (RA). However, a specific approach to detect patients at higher risk of prosthetic joint infection (PJI) and mechanical complications is absent. The aim of this study is to identify groups at higher risk for infections and mechanical complications after TJA in patients with RA and OA based on their most significant predictors. This is a hospital-based cohort study with 1150 recipients of TJA. Risk factors and comorbidities were assessed prior to the index surgery. Multivariate logistic and hazard regression were used to determine the relationship between risk factors and occurrence of complications after TJA. Odds ratios (OR), hazard ratios (HR), 95% confidence intervals (CI), and comparison between areas under the curve (AUC) using DeLong’s method are presented. Complications were more frequent in subjects with RA, use of corticosteroids, and previous comorbidities: respiratory disease, infections, diabetes, anemia, mental and musculoskeletal comorbidities than in subjects without these risk factors, and these factors were predictors of infections and mechanical complications (P < 0.05). A model including these factors was superior to a model with only type of joint disease (OA/RA) or age and gender to detect infections or mechanical complications after TJA (P < 0.05 for difference between models). Complication risk proportionally increased with the presence of two or more comorbidities (P < 0.001). There are two groups at higher risk for infections after TJA: patients with OA with at least two risk factors and patients with RA, who usually present at least one of the risk factors for infection.