Background Multi-drug resistant tuberculosis (MDR-TB) treatment involves toxic drugs that cause adverse-drug-effects (ADEs), which are life threatening and may lead to death if not well managed. In Uganda, the prevalence of MDR-TB is increasingly high and about 95% of the patients are on treatment. However, little is known about the prevalence of ADEs among the patients on MDR-TB medicines. We therefore estimated the prevalence of ADEs of MDR-TB drugs and factors associated with ADEs in two health facilities in Uganda. Methods Between March and November 2021, we conducted a retrospective cohort study of MDR-TB patients enrolled at Mulago national referral and Mbarara regional referral hospitals in Uganda. We reviewed files of MDR-TB patients enrolled between January 2015 and December 2020. We extracted data on ADEs, defined as irritative reactions to MDR-TB drugs. We conducted descriptive analysis and modified Poisson regression analysis to determine factors associated with ADEs. Results A total of 856 files were reviewed. Overall, 369 (43.1%) of 856 patients had ADEs and 145 (17%) of 856 suffered from more than one. The most recorded effects were: joint pain (244/369 (66%)); hearing loss (75/369(20%)); and vomiting (58/369(16%)). Patients started on the 24 months regimen (adjusted prevalence ratio (adj.PR=1.4, 95%; 1.07, 1.76) and individualized regimens (adj.PR=1.5, 95%; 1.11, 1.93) were more likely to suffer from ADEs. Lack of transport for clinical monitoring (adj.PR=1.9, 95%; 1.21, 3.11); alcohol consumption (adj.PR=1.2, 95%; 1.05, 1.43), and receipt of directly-observed-therapy from peripheral health facilities (adj.PR=1.6, 95%; 1.10, 2.41) were significantly associated with experiencing ADEs. However, patients who received food supplies (adj.PR=0.61, 95%; 0.51, 0.71) were less likely to suffer from ADEs. Conclusion Adverse-drug-effects were high among MDR-TB patients and joint-pains was the commonest effect. Interventions such as provision of food supplies, transport and consistent counselling on alcohol consumption to patients at initiation treatment facilities may reduce ADEs