Objective The aim of the study was to assess the time effect of intra-articular injection with triamcinolone hexacetonide in rheumatic patients. Design A prospective case-control study with patients submitted to one intra-articular injection with triamcinolone hexacetonide. Patients were followed monthly (12 mos) for pain and swelling. Results Two hundred sixty-two joints were assessed in 158 patients with mean ± SD age of 60 ± 13.7 yrs. Remission was observed at 3, 6, and 12 mos in 142 (54.19%), 111 (42.36%), and 105 (40.07%) joints, respectively. The mean ± SD time effect were 8 ± 4.0 mos; 8.4 ± 3.9 for rheumatoid arthritis patients and 6.9 ± 4.0 for osteoarthritis patients (P = 0.012) and 10.4 ± 2.7 mos for small, 7.7 ± 4.1 for medium, and 6.8 ± 4.0 for large joints. The joints were divided into two groups: long-term group (time effect of intra-articular injection longer than 6 mos) and short-term group. The following are the variables associated (P < 0.05) with long-term group: rheumatoid arthritis, small and medium-sized joints, female sex, lower pain and swelling visual analog scale scores, and use of leflunomide. The following are the variables associated with short-term group: receiving only one intra-articular injection, hypertension, diabetes mellitus, and biological therapy. Conclusions The mean ± SD time effect of intra-articular injection with triamcinolone hexacetonide was 8.0 ± 4.0 mos. The associated predictors were rheumatoid arthritis, small and medium joints, lower pain/swelling visual analog scale scores, and use of leflunomide.