A study evaluates the effectiveness of non-pharmaceutical interventions (NPIs) used globally to control the spread of SARS-CoV-2. The research analyzes 6,068 hierarchically coded NPIs implemented in 79 territories, assessing their impact on the effective reproduction number, Rr. The study combines four computational techniques—case-control analysis, LASSO regression, random forests, and transformers—to evaluate the effectiveness of NPIs. The findings show that a combination of NPIs is necessary to curb the spread of the virus, with less disruptive measures being as effective as more intrusive ones. The study also highlights the importance of timing and local context in determining the effectiveness of NPIs. Results indicate that measures such as social distancing, travel restrictions, and border controls are among the most effective. However, some NPIs, like environmental cleaning, are less effective. The study also finds that risk-communication strategies and government support for vulnerable populations are highly effective. The research emphasizes the need for tailored NPIs based on local conditions and the importance of considering the sequence and timing of interventions. The study concludes that no single NPI is sufficient to control the spread of the virus, and a combination of measures is necessary for effective control. The findings also highlight the importance of data collection and the need for further research to improve the understanding of NPI effectiveness.A study evaluates the effectiveness of non-pharmaceutical interventions (NPIs) used globally to control the spread of SARS-CoV-2. The research analyzes 6,068 hierarchically coded NPIs implemented in 79 territories, assessing their impact on the effective reproduction number, Rr. The study combines four computational techniques—case-control analysis, LASSO regression, random forests, and transformers—to evaluate the effectiveness of NPIs. The findings show that a combination of NPIs is necessary to curb the spread of the virus, with less disruptive measures being as effective as more intrusive ones. The study also highlights the importance of timing and local context in determining the effectiveness of NPIs. Results indicate that measures such as social distancing, travel restrictions, and border controls are among the most effective. However, some NPIs, like environmental cleaning, are less effective. The study also finds that risk-communication strategies and government support for vulnerable populations are highly effective. The research emphasizes the need for tailored NPIs based on local conditions and the importance of considering the sequence and timing of interventions. The study concludes that no single NPI is sufficient to control the spread of the virus, and a combination of measures is necessary for effective control. The findings also highlight the importance of data collection and the need for further research to improve the understanding of NPI effectiveness.