Abstract Background Several multinational cancer research collaborative organizations have been formed recently in Latin America in an effort to increase clinical research and the enrollment of patients in clinical trials, including the Latin American Cooperative Oncology Group (LACOG), established in 2012, and the Latin American Consortium for Lung Cancer Research (CLICaP), established in 2010. The aim of this study is to characterize changes in lung cancer clinical trial participation in Latin America before and after 2012. Methods Clinical trials were identified in clinicaltrials.gov using the search terms “lung cancer,” country filters for 21 Latin American countries, and study start dates 01/01/2001-12/31/2011 and 01/01/2012-12/31/2021. Clinical trials were categorized as either originating in Latin America (LA) or outside Latin America with participation of Latin American countries (non-LA). The number of trials, trial phase, driver mutation studied, and types of intervention were collected for each country. Descriptive statistics and chi-square analysis with 95% confidence intervals were calculated. Result: Our analysis included 426 clinical trials involving Latin American countries, of which 74% (317/426) were phase 3 trials. Only 6% (26/426) of the trials from 2001-2021 were LA trials. Comparing the period 2001-2011 to 2012-2021, there was a marked increase in total clinical trials (101 v. 325, p<0.001), predominantly due to an increase in non-LA trials (87 v. 313, p<0.001). The number of LA trials was unchanged between the two periods (14 v. 12, p=0.69). There was an increase in the percentage of phase 3 trials (60% v. 79%, p<0.001) between the two periods. There was also an 83% increase in studies for patients with specific driver mutations (EGFR, KRAS, ALK, and RET) (53 v. 97, p<0.001). The countries with the highest rates of open clinical trials were Brazil, Mexico, and Argentina. In all three countries, the total number of clinical trials increased between the period 2001-2011 and 2012-2021: Mexico (40 v. 88, p<0.001, 120% increase), Brazil (61 v. 108, p=0.003, 77% increase), and Argentina (50 v. 78, p=0.013, 56% increase). Conclusion Overall, there was a significant (>3-fold) increase in clinical trial participation by Latin American countries, specifically in non-LA trials, from 2012-2021. This increase may correspond to the organization of CLICaP and LACOG, which are multinational cancer research organizations in Latin America. However, there were few LA trials. More LA studies are therefore needed to confidently extrapolate the results of global clinical trials to patients in Latin America. Citation Format: Thomas M. Knapp, Joseph Nygaard, Joshua Cassinat, Priya Gopalan. Lung cancer clinical trials in Latin America: A 20-year analysis. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5529.