Background: The present meta-analysis was carried out to assess the risk of infection and other side effects after anti TNF- α use to treat Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis. Methods: To assess the impact of anti-TNF medicines on the prevalence of infectious adverse events (serious infections; tuberculosis; opportunistic infections; any infection; risk of cancer), we performed a meta-analysis. We searched PubMed, Cinahl (via Ebsco), Scopus, and Web of Sciences databases for trials comparing anti-TNF medications to placebo or no therapy in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis from August 2006 to August 2020. A total of 27 articles were used for the data analysis. The risk of bias (RoB) in included studies was evaluated using the QUADAS-2 tool. The odds ratio of these studies was used to construct the forest plot. The random-effects model was used to pool the data. Also, the random-effects model was used with statistical significance at a p-value less than 0.05 to assess the risk of infections and cancer after anti-TNF treatment. Results: The risk of developing cancer (OR=1.13; 95% CI 0.79 to 1.62; p<0.05) which is lesser than serious infections (OR= 1.5; 95% CI 1.0257 to 2.2276; p<0.05) after anti TNF treatment. However, the risk of developing tuberculosis infection is highest in the patients on anti-TNF treatment (OR=3.96; 95% CI 2.87-5.45) followed by skin and soft tissue infections, i.e. (OR= 2.4598; 95% CI 1.0481 to 5.7732; p<0.05). Conclusion: With the growing use of TNF inhibitors in adult patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, it is critical to keep track of their safety profiles using additional resources (e.g., registries and long-term epidemiological studies). The present meta-analysis is recent evidence which suggests that there is a definite high risk of tuberculosis and cancer after anti-TNF treatment.