Background: Occupational insecticidal poisoning (OIP) is a global phenomenon, which is even more prevalent among indoor residual sprayworkers and this can pose a serious threat to their health. Objectives: This study aimed to assess spray-workers' management of insecticide risk indicators and occupational insecticidal poisoning. Materials and Methods: An analytical cross-sectional survey was adopted, that involved all of the professional indoor residual spray-workers serving in the Omo-Nada woreda (district), Ethiopia. The survey was conducted between January and April 2011 by administering a pretested questionnaire. All statistical analyses were performed by using SPSS v.19.0. A two-sided Fisher's exact test was performed to determine associations between the variables. Results: Overall, 52.4% of the study participants had an awareness of the usage of personal protective equipment (PPE), whereas 41.9% were unable to read the pesticide labels. About 75.3% of spray-workers never drink or eat or smoke, while spraying. Statistical analysis (two-sided Fisher's exact test) confirmed that there is no statistically significant association between safe insecticide practice with the spray-worker's gender (P = 0.332), whereas, there were strong correlations found with age (P = 0.001), educational status (P = 0.001) and years of work experience (P = 0.001). Conclusions: Despite adequate awareness of safe insecticide management, most of the spray-workers were observed to be reluctant to put this knowledge into practice, either due to the inadequacy of PPE or negligence. Furthermore, a sizable faction of these workers still had limited knowledge and erroneous risk perceptions, thus increasing their risk of OIP. Therefore, appropriate communication strategies and training could reduce the occupational risk of insecticide exposure, which would ultimately minimize the related health hazards of insecticidal poisoning.