Opioid-induced constipation (OIC) is the most prevalent side effect of methadone maintenance therapy (MMT). Naloxone could reduce the OIC. Fifty-six MMT cases (< 75mg/day methadone, > 3months) were entered randomly into four groups of a trial. They received placebo or naloxone tablets (0.5, 2, or 4mg/day) once a day for 2weeks. They continued their conventional laxative. Their constipation and opiate withdrawal (OWS) were evaluated by the Bristol Stool Form Scale (stool consistency and frequency), Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire, Constipation Scoring System (CSS), and the Subjective Opiate Withdrawal Scale (SOWS) before starting treatment and at the end of the first and second weeks. The dose of 4mg/day naloxone was excluded from the study due to severe OWS. The precipitantsof groups had similar ages, methadone dose and duration, laxative use, and constipation scores at the start of the trial. However, 2mg of naloxone could change the stool consistency (PV = 0.0052) and frequency (P = 0.0133), 0.5mg/day dose only improved the stool consistency (P = 0.0016). The patients' CSS and PAC-SYM scores were reduced by naloxone after the 1st week of treatment. However, there was no significant difference in the mean score of SOWS at different assessment times and groups. Also, 3 and 4 cases of 0.5 and 2mg/day groups, respectively, withdrew from the study due to OWS. Oral naloxone at doses of 0.5 and 2mg/day was significantly more effective than placebo on OIC in MMT. However, the dose of 4mg induced intolerable OWS.