Objectives: Tuberculosis is a major cause of global morbidity and mortality. Statins could be associated with a lower risk of some infectious diseases, including tuberculosis. Statins could reduce the risk of latent tuberculosis infection and active tuberculosis, acting as an adjuvant in treating tuberculosis. This study aimed to determine if statins reduce the risk of active tuberculosis. Methods: We systematically analyzed 8 databases from inception to December 2021. We included articles without language restriction if they met our inclusion and exclusion criteria and the PECO strategy (Population: adults without active pulmonary tuberculosis; Exposure: treatment with any statin; Comparator: no use of statins; Outcome: active tuberculosis). Odds Ratios (ORs) with 95% confidence intervals (CIs) were pooled using random-effects models regardless of heterogeneity quantified by Cochran’s Q and I2 statistics. We performed subgroup analyses according to the participants’ diabetic status and follow-up length (≤10 years or >10 years). Results: Twelve articles reporting observational studies involving 3.038.043 participants, including at least 32.668 cases of active tuberculosis. Eight reported retrospective cohort studies, three nested case-control study, and one was a case control study. According to our meta-analysis, statins may reduce the risk of active tuberculosis, in the general population (OR 0.66; 95% CI, 0.54-0.81), in non-diabetic (OR 0.66; 95% CI, 0.54-0.80) and in diabetic patients (OR 0.65; 95% CI, 0.49-0.87). This protective effect did not differ according to the participants’ diabetic status nor follow-up length (test for subgroup differences I2=0). We found significant clinical and methodological heterogeneity. Similarly, the forest plot, and the I2 and Chi2 statistics suggested considerable statistical heterogeneity (I2=95%, p<0.05, respectively). Of the 12 included studies, 9 were at low risk of bias and 3 were at high risk of bias. Similarly, according to the funnel plot, it is very likely that there are important publication biases. Conclusion: Statin use may significantly reduce the risk of tuberculosis in the general population, diabetic and non-diabetic patients. Nevertheless, caution should be exercised when interpreting these conclusions, due to the quality of the evidence, the heterogeneity of the studies, the presence of bias, and the difficulty in extrapolating these results to populations of other races and ethnicities.