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Alopecia areata (AA) is a common disease characterized by hair loss with an autoimmune background. There are many lines of therapy, but no standard line for all cases. Consequently, treating severe forms of AA is challenging. This study aimed to compare the efficacy and safety of the combination of diphenylcyclopropenone (DPCP) and platelet-rich plasma (PRP) with DPCP alone in treating patients with severe or refractory AA. Our randomized clinical trial was conducted on patients with severe and recalcitrant AA. Group A included 13 patients who received only DPCP, while Group B included 11 patients who received both DPCP and PRP. After sensitization in both groups of patients, DPCP was applied to half the scalp weekly. In addition, PRP injection in all scalp was performed once a month in group B. The patients in both groups completed the study for six months. The regrowth scale results were 53.85% and 54.5% for groups A and B, respectively. Although the response rate of group B was higher than that of group A, there is no statistically significant difference between the two groups. From our clinical trial, it can be concluded that DPCP alone or combined with PRP is an effective and safe method for treating severe or recalcitrant AA.