OBJECTIVE：To compare the anesthetic effect and safety of dexmedetomidine hydrochloride and propofol in painless colonoscopy. METHODS：80 patients who underwent painless colonoscopy was retrospectively analyzed and divided into group A and group B. Group A was given loading dose of 1 mg/kg propofol within 30 s and maintained with 6 mg/（kg·h）；group B was given loading dose of 0.3 μg/kg Dexmedetomidine hydrochloride injection by micropump for slow pumping 5 min and maintained with 0.2-0.3 μg/（kg·h）. Mean arterial pressure（MAP），heart rate（HR），oxygen saturation（SpO2）and respiratory rate（RR）before examination（T0），before microscopic examination（T1），1 min（T2）and 10 min（T3）after microscopic examination，1 min （T4）and 5 min（T5）after colonoscopy withdrawal，onset time of anesthesia，entry time，examination time and discharge time，patients with adjunctive use of fentanyl and incidence of adverse reactions in 2 groups were observed. RESULTS：MAP in group A at T1 was significantly lower than T0，HR in 2 groups at T1-T3 was significantly lower than T0，the differences were statistically significant（ P＜0.05），however，there were no significant differences in the SpO2 and RR between 2 groups（P＞0.05）. Onset time of anesthesia， patients with adjunctive use of fentanyl and incidence of adverse reactions in group B were significantly lower than group B，the differences were statistically significant（P＜0.05）. CONCLUSIONS：Both dexmedetomidine hydrochloride and propofol has good anesthetic effect in painless colonoscopy，but dexmedetomidine has better safety.