ABSTRACT Background: Malaria is an acute febrile parasitic disease that significantly impacts global public health. In Brazil, the most studied endemic area for the disease is the Amazon region. This study aims to analyze temporal, spatial, and spatiotemporal patterns of malaria in the extra-Amazon region of Brazil over a 22-year period. Methods: We conducted a time-series study from 2001 to 2022, encompassing both autochthonous and imported cases. Time trend analysis was employed to assess fluctuations in incidence rates over the years. Spatial clusters of infection risk were identified using the Local Moran Index and Kulldorff's scan. Results: A total of 18,633 malaria cases were identified in the extra-Amazon region, including 1,980 autochthonous, 13,836 imported, and 2,817 of unknown origin. During the first period (2001-2011), 1,348 autochthonous and 9,124 imported cases were reported. In the second period (2012-2022), there were 632 autochthonous and 4,712 imported cases. The state of Espírito Santo exhibited a decreasing trend but maintained the highest incidence rates throughout the study. The number of municipalities at high risk for autochthonous cases declined, with Espírito Santo, Minas Gerais, and Piauí having the most municipalities with high rates. For imported cases, the federative units with the highest numbers in both periods were Ceará, Distrito Federal, Goiás, Minas Gerais, Piauí, and Paraná. Conclusions: The data reveal the areas most affected by malaria and thus of highest priority for implementing control strategies. Background health temporal spatial extraAmazon extra 22year year 22 Methods timeseries time series 200 2022 years Kulldorffs Kulldorff s scan Results 18633 18 633 18,63 1980 1 980 1,98 13836 13 836 13,83 2817 2 817 2,81 origin 20012011, 20012011 2011 , (2001-2011) 1348 348 1,34 9124 9 124 9,12 reported 20122022, 20122022 2012 (2012-2022) 63 4712 4 712 4,71 declined Gerais Ceará Federal Goiás Paraná Conclusions strategies 20 202 1863 18,6 198 98 1,9 1383 83 13,8 281 81 2,8 2001201 201 (2001-2011 134 34 1,3 912 12 9,1 2012202 (2012-2022 6 471 71 4,7 186 18, 19 1, 138 8 13, 28 2, 200120 (2001-201 3 91 9, 201220 (2012-202 47 7 4, 20012 (2001-20 20122 (2012-20 (2001-2 (2012-2 (2001- (2012- (2001 (2012 (200 (201 (20 (2 (