Objective: To determine the efficacy of 1% Ivermectin and 5% Permethrine in clinically positive cases of scabies after overnight topical applications of each drug. Study Design: Randomized Comparative study. Setting: OPD of the Department of Dermatology, THQ Hospital Kabirwala, Punjab, Pakistan. Period: 1st January to 31st March 2020. Material & Method: A total of 276 patients of either sex with typical signs of scabies (papules, nodules, vesicles, classical burrows and nocturnal pruritus) were selected and were randomly divided into two groups A and B, with 138 patients in each group. Patients of Group A were supplied Ivermectin 1% lotion and patients of group B were supplied Permethrin 5% lotion for topical application at night all over the body except face and this treatment was repeated after 7 days. After the 4-week post-treatment follow-up period, data for 185 patients (Group A=89, Group B=96) were analyzed statistically for comparative efficacy of each drug by applying Chi-square test statistics. Results: Demographic information showed that higher (P<0.05) occurrence of the disease (44.9%) was observed in patients between 21-30 years of age. Difference between patients belonging to the urban/rural area (105/80), lower/middle class (104/81), gender (Male/Female) 87/98, marital status (married/un-married) 129/56 was significant (P<0.05). Moreover, among the patients of various occupations, highest frequency (34.6%) was observed in house wives and the lowest (10.8%) was in laborers (P<0.05). Highest number of patients (33%) reported 15-30 days after they first noted signs of disease, while lowest number (9.7%) reported the problem >30 days after appearance of the disease (P<0.05). Difference between patients sh owing moderate/severe signs of scabies (88/97), history of close-contact/no-contact (65/120), showing high night-itch/no-itch (180/5), have signs of burrows with jet trail/no burrows (130/55) were significant (P<0.05), and 62.7% patients had less than 10 lesions. Cure rate reco.rded at 8th day, was 66.3 and 70.8% for Ivermectin and Permethrin, respectively, difference was non-significant. At day 14, 21 and at day 28, cure rate in patients treated with Ivermectin 1% was 85.4, 94.4 and 94.9%, respectively, and for patients treated with Permethrine 5% was 86.5, 99.0 and 99.3%, respectively, differences were non-significant. However, both of the treatments resulted in significantly (P<0.01) increased cure rate after day-8 to day-28th, being 66.3 to 94.4% and 70.8 to 99.3%, respectively. Both therapies resulted (P<0.05) recovery within 8 to 21 days after treatment from severity of signs, having contact history, presence of night itch, number of burrows/jet with trail and number of lesions, while difference between the therapies was non-significant. Conclusion: Topical application of Ivermectin (1%) and Permethrine (5%) lotion was equally effective by curing the patients having moderate to severe signs of scabies when applied twice at 7 days interval, and results in significant (P<0.01) increase in cure rate at 4th week.