Background: The farmers' habit of pesticide management is an important factor in recovering the farmer's health from contamination. Most farmers have poor knowledge of pesticide safety management. Aims: This study aimed at analyzing factors related to the blood Acetylcholinesterase level as an indicator of pesticide contamination in the body.Settings and Design: This research was a cross-sectional study involved 57 people of rice and horticulture farmers in Ponorogo. The independent variables were age, working years as a farmers, educational background, activity, combination of pesticides, read the direction, storage and mixing, get information about pesticide safety management, use of PPE, smoking habit, mixing inorganic and organic, and personal hygiene. The dependent variable was blood acetylcholinesterase level. Methods and Material: The independent variables were observed by questionnaire and the dependent variable was measured with a photometer by the cobast method. The pesticide levels divided into four categories: (1) Veryhigh risk of poisoning: 5-6 U/L; (2) High risk of poisoning: 7-8 U/L; (3) Medium risk of poisoning: 9-10 U/L, and (4) Low risk of poisoning : 11-12 U/L. Statistical analysis used: The data were analyzed by multiple linear regressions.The correlation within variables are analysed using Pearson Correlation test with 95 % of Confidence Interval (CI). The Statistical Package for Social Sciences (SPSS) 24 software were used in this research. Results: There were 6 farmers at very high risk, 17 farmers at high risk, 26 farmers at medium risk, and 8 farmers at low risk of pesticide contamination. The independent variable contributed 32.2% (R Square = 0.322) to the blood acetylcholinesterase level. The influencing factor was combination of pesticide (p-value = 0.02).Conclusions: Combination of pesticide was the crucial factors in pesticide safety management. Farmers should do pesticide safety management properly start from storage, mixing, handling, spraying, and disposing of. Keywords: Acetylcholinesterase, farmer, pesticide, associate factor Key Messages: The use of pesticides in combination was simultaneously affecting acetylcholinesterase levels in the blood. Farmers use pesticides based on hereditary experience can increasing pesticide contamination. Pesticide safety managementwere key factors in preventing pesticide exposure