This research aims to evaluate the use of selective cyclooxygenase-2 inhibitor anti-inflammatory drugs in Brazil and the scientific evidence on the safety of these drugs. Four main approaches will be used: (1) systematic review with meta-analysis, (2) analysis of national consumption trends, (3) international and (4) national pharmacovigilance. (1) Randomized controlled trials that assessed renal effects of coxibs (celecoxib, etoricoxib, lumiracoxib, parecoxib, and valdecoxib) were searched in PubMed, Embase, Scopus and other sources up to March 2024. Two independent reviewers performed study screening, data extraction, and risk of bias assessment. Random effect meta-analysis was employed to calculate the relative risks (RR) and 95% confidence intervals (CI) of renal effects of coxibs compared to placebo and inconsistency among studies (I2). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. (1.1) A cross-sectional analysis based on a previous systematic review on the renal adverse effects of coxibs. Studies were assessed for selective outcome reporting considering the item #6 of the Cochrane Risk of Bias tool. RCT that reported only predefined adverse events or if they reached an incidence threshold were categorized as at high risk. We collected the 2022 Journal Impact Factor (JIF), length of peer review, location, type of coxib, and funding. (2) A time trend analysis of coxibs sales in Brazil from January 2014 to December 2021 was conducted using the Brazilian National Controlled Products Management System. Primary outcomes consisted of coxibs sales in defined daily dose (DDD) and DDD per 1000 inhabitants per day (DID), analyzed by Brazilian region (North, Northeast, South, Southeast, and Midwest). The trends in coxib consumption were analyzed using a segmented regression model, and the average annual percent change (AAPC) with a 95% confidence interval (95% CI) was calculated.