Malaria is a major public health problem in French Guiana. This study was conducted in children <1-5 years of age in Camopi, an Amerindian village in eastern French Guiana. Medical, environmental, and behavioral predictive factors of malaria were studied using the Kaplan-Meier method and Cox modeling. Variables included were clearing vegetation around the home (hazard ratio [HR] = 0.62, 95% confidence interval [CI] = 0.43-0.88 for 50-75% cleared and HR = 0.5, 95% CI = 0.31-0.81 for > 75% cleared) relative to homes surrounded by vegetation; distance of a home from a river (HR = 0.56, 95% CI = 0.37-0.85 for distances between 20 and 40 meters, HR = 0.72, 95% CI = 0.47-1.09 for distances between 40 and 80 meters, HR = 0.52, 95% CI = 0.28-0.94 for distances between 80 and 120 meters, and HR = 0.5, 95% CI = 0.30-0.86 for distances > 120 meters) relative to distances < 20 meters; the number of occupants in the home (HR = 1.54, 95% CI = 0.98-2.44 for 7 occupants, HR = 1.9, 95% CI = 1.29-2.81 for 8-11 occupants, and HR = 2.03, 95% CI = 1.27-3.23 for > 11 occupants); clothing (HR = 0.64, 95% CI = 0.46-0.90 for children wearing western-style clothes relative to those wearing the traditional kalimbe), and ethnicity (Wayampi children had a lower hazard of malaria relative to Emerillon children: HR = 0.55, 95% CI = 0.40-0.80). The environment near the home was strongly associated with malaria. This suggests that simple pragmatic protection measures would be useful in Camopi.