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Purpose: This study aimed to explore professional autonomy, nursing work environment, and clinical decision making ability and to determine predictors of clinical decision making ability among clinical nurses. Methods: A cross-sectional design was used in this study and 263 clinical nurses were selected from advanced-level hospitals with over 500 beds located in D metropolitan city. Independent t-test, ANOVA, Pearson’s correlation coefficients and hierarchical multiple regression analyses were done with the SPSS/WIN 20.0 program. Results: Clinical nurses reported moderate levels of professional autonomy, nursing work environment and clinical decision making ability. Marital status, professional autonomy and nursing work environment accounted for 25% of variance in clinical decision making ability required in various clinical settings. Importantly, being married, higher level of professional autonomy, and greater satisfaction with work environment were significantly associated with better decision making ability. Conclusion: Findings indicate that improving the quality of decision making in the healthcare settings requires awareness of the multiple effects of individual, occupational and environmental features. Nurses’ ability to make effective clinical decisions may rely on personal characteristics, the degree of autonomy in their job, and nurses’ satisfaction with their work environment.