Although there is ample evidence that intra-articular injuries are associated with the up-regulation of pro-inflammatory cytokines, the success of anti-inflammatory, disease-modifying treatments to prevent posttraumatic osteoarthritis (PTOA) remain uncertain. To summarize the current status of anti-inflammatory therapy for PTOA, we conducted a systematic review. 9 clinical studies in humans were identified applying anti-inflammatory agents to prevent or treat PTOA. A total of 347 patients aged an average 41 ± 14 years were included in this review. 5 studies had comparable designs with randomized allocation. Those studies of course had a statistically significant higher Coleman Methodology Score (65 ± 6) than the case-control studies (39 ± 13, p = 0.013). The most frequently reported main outcome parameter was pain assessed by different scales (n = 7), the most examined joint the knee (n = 7). The majority of the analyses (n = 6) focused on the intra-articular (IA) application of hyaluronic acid (HA) reporting mainly positive effects. One study stated positive results following IA administration of Interleukin 1 receptor antagonist in -patients presenting rupture of the anterior cruciate ligament. Platelet-rich plasma was also used to relieve symptoms following acute injury, but the study quality was too low to conclude any effects. Although the initial data, especially regarding IA HA injection, are encouraging, study designs differ substantially. Therefore, current data does not allow us to conclude that anti-inflammatory therapy following acute injuries has beneficial effects on short- or long-term outcomes.