Topical calcineurin inhibitors have proved to be suitable for the treatment of AD. We conducted a meta-analysis comparing efficacy and tolerance of tacrolimus with pimecrolimus in treatment of AD. According to our meta-analysis, tacrolimus 0.1% was more effective than pimecrolimus 1% in adult patients (week 3: risk ratio [RR] 0.55, 95% confidence interval [CI] 0.42–0.73), and tacrolimus (a combination of 0.03% and 0.1%) was also more effective than pimecrolimus 1% in pediatric patients (week 6/end of study: RR 0.76, 95% CI 0.63–0.92). Regardless of age or illness severity, tacrolimus 0.1% had higher efficacy than pimecrolimus 1% in the treatment of AD (week 3: RR 0.55, 95% CI 0.42–0.72). In adult patients, tacrolimus 0.1% had more adverse events than pimecrolimus 1% (RR 1.30, 95% CI 1.02–1.66), but the incidence of adverse events between tacrolimus 0.1% (or 0.03%) and pimecrolimus 1% was not significantly different in pediatric patients. No matter whether the patients were adult or pediatric, more pimecrolimus-treated patients withdrew from the trials because of a lack of efficacy. Regardless of age and illness severity, more pimecrolimus 1%-treated patients withdrew from the trials because of a lack of efficacy, compared with tacrolimus 0.1% (or 0.03%)-treated patients. More pimecrolimus-treated pediatric patients withdrew from the trials because of adverse events (RR 0.26, 95% CI 0.1–0.68). More pimecrolimus 1%-treated patients withdrew from the trials because of adverse events, compared with tacrolimus 0.03%-treated patients, regardless of age (RR 0.1, 95% CI 0.02–0.53). In conclusion, tacrolimus ointment has higher efficacy and better tolerance than pimecrolimus cream in treatment of AD.