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Prurigo nodularis (PN) is a chronic, benign neurodermatitis of unclear etiology characterized by excoriated, intensely pruritic nodules secondary to an intense itch-scratch cycle. PN treatment is still a challenge, and it is frustrating for both dermatologists and patients. The evidence for the effectiveness of a readily available treatment like cryotherapy is limited. To compare the efficacy of cryotherapy vs 0.05% clobetasol propionate in PN patients attending the RDTC, Northern Tanzania, from October 2018 to July 2019. Based on previous year data, it was expected to enroll nine patients. Assent and consent were obtained. Fourteen patients were enrolled, 11 analyzed; intra-subject control done each one-half of the body received either intervention randomly. The cryotherapy was given in two cycles from 5 to 10 s in one session and clobetasol propionate was applied twice daily for 4 weeks. The patients were followed-up weekly by telephone reminded them to apply clobetasol. Data entry and analysis was done in SPSS version 20. Ethical considerations were observed. Eleven patients were analyzed; four (36%) males and seven (64%) females. Cryotherapy had nodule clearance in the 11 patients of 75% to 100% in 11 (100%) and clobetasol propionate only in three of the patients. Seven patients (63.6%) preferred cryotherapy. Cryotherapy preferred above clobetasol propionate.