Rituximab has been tried increasingly for the treatment of pemphigus vulgaris (PV). However, there is still no consensus about its dosing regimens, efficacy, and side effects due to insufficient clinical trials. The goal of this study was to evaluate its efficacy in the treatment of PV. This is a case series of patients with PV who received rituximab, four doses of 375 mg/m2 intravenously weekly, plus concomitant oral prednisolone. The primary outcomes were the rate of initial clinical improvement and marked clinical improvement; secondary outcomes included prednisolone doses (mg/d) at baseline, three months, six months and the last visit, as well as the side effects. Forty out of 45 patients completed the study. The mean follow-up time was 12 ± 10.69 months (range of 3–46 months). Following treatment with rituximab, all the analyzed patients with PV had initial clinical improvement after a mean period of 6.35 weeks and a marked clinical improvement after a mean of 10.13 months. The mean prednisolone dose (mg/d) decreased significantly from a baseline level of 48.75 ± 25.86 to 26.50 ± 12.95 at three months, 20.70 ± 17.51 at six months, and 15.26 ± 9.98 at the last visit (P = 0.0001). The encountered side effects following rituximab were lung abscess, sepsis, pneumonia, cavernous sinus thrombosis, skin abscess, deep vein thrombosis, generalized arthralgia, and Stevens–Johnson syndrome. According to our study, rituximab may be an effective adjuvant to prednisolone for the treatment of PV; however, its safety profile remains concerning. (IRCT registration number: IRCT201111022704N2.).