BackgroundLeprosy is still a disease of public health concern. Globally, 2–3 million people are thought to be affected by leprosy’s disease-related disabilities. Regarding leprosy status in Zanzibar, limited information is available. Determining changes in detection rates and factors associated with disability is crucial for treatment and preventative strategies for this debilitating disease. This study aimed to determine trends in case detection rate for leprosy and risk factors for disability among registered patients in Zanzibar, from 2018 to 2021. The study included all leprosy patients who received treatment in Zanzibar's 11 districts between 2018 and 2021. The study design used was an analytical cross-sectional. Prevalence and new case detection rate (NCDR) were calculated. Multivariable Poisson regression analyses were used to identify factors associated with leprosy disability. Crude and adjusted prevalence ratios (APR) and their respective 95% confidence intervals (CI) were reported. P-values ≤ 0.05 were considered significant.ResultsOf the 490 leprosy cases reported between 2018 and 2021, 469 (95.7%) were new patients, and 349 (71.2%) were multi-bacillary. The disease was found to be more common in males 296 (60.4%). The average prevalence was 7/100,000 population, while the average NCDR was 7/100,000 from 2018 to 2021. There was a significant decrease in disability grades from diagnosis to the end of treatment over 4 years (P < 0.001). Male sex (APR 1.55; 95% CI 1.18–2.04), advanced age (APR 5.01; 95% CI 1.91–13.17), multi-bacillary (APR 6.99; 95% CI 3.16–15.44) and HIV negative patients (APR 1.51; 95% CI 1.11–2.06) were more likely to develop physical disability.ConclusionThis study found that leprosy disability grades at diagnosis compared to the end of treatment declined during 4 years. There was no significant change in point prevalence and NCDR during the 4-year study period. Disability was associated with male sex, advanced age, multi-bacillary, and HIV-negative patients. To prevent leprosy-related disability and transmission, health education, early case detection, and adequate multidrug therapy should be prioritized.