A farmer-led protected zero-grazed dairy cattle initiative, involving pyrethroid treated netting around zero-grazing cowsheds, was implemented over a four-year period in tsetse-infested areas of Southeast Uganda. The pyrethroid treated netting was intended to prevent dairy cattle against tsetse bites and consequently transmission of trypanosomosis, while boosting milk production as an economic venture. A longitudinal study was conducted in six districts, including Budaka, Busia, Iganga, Manafwa, Mayuge and Tororo, during which a total of 184 protected zero-grazing units holding 289 dairy cattle were visited five times. The prevalence of trypanosomosis, mortality, mean packed cell volume (PCV), status of netting, spraying practices, and pasture and legume feed status, cowshed hygiene status, and milk yield were monitored. The findings revealed low prevalence of trypanosomosis among dairy cattle (1.0-5.5%), due to Trypanosoma brucei (0.0-0.4%), Trypanosoma congolense (0.0-0.7%) and Trypanosoma vivax (0.4-3.4%) infections. Only 25 adult cattle and 40 calves were reported dead. Dairy cattle had good health, given high mean PCV values (27.7 - 30.6). 99.2% and 100.0% of the zero-grazing units had lost netting by visit IV and V, respectively. By the second to the fourth year, prevention of dairy cattle from tsetse or tick bites hugely relied on spraying because all zero-grazing units had lost netting. Dual tsetse and tick control was practised by 66.9% of the 184 zero-grazing units, while only 33.1% of the units applied tick-selective control. Correct spraying intervals were observed by 57.8% of the zero-grazing units. Most zero-grazing units (range 67.9-97.5%) had sufficient pasture, while few units (range 17.9-34.8%) had sufficient legumes. Poorest cowshed hygiene was observed in zero-grazing units in Budaka district (93.1%), followed by Busia district (33.3%), Iganga district (31.1%), Mayuge district (12.1%), Tororo district (10.0%) and Manafwa district (6.3%).The best average milk yield per cow per day was registered in Iganga district (6.2 L-8.7 L), followed by Mayuge district (4.5 L- 8.2 L), Manafwa district (4.5 L-6.2 L), Busia district (4.0 L-6.3 L), Tororo district (3.3 L-6.7 L), and Budaka district (3.7 L-6.0 L). Overall average milk yield per cow per day of 5.0 L to 6.4 L across visits with a minimum of 0.5 L and maximum of 19.0 L per cow per day were achieved. In conclusion, pyrethroid treated netting around zero-grazing units supplemented with spraying of cattle effectively protected dairy cattle against trypanosomosis and maintained their good health. However, farmers’ observation indicated that as netting became older, it became more fragile. Larger nets of 1.5 m high had a longer duration of 6 to 8 months than smaller nets of 1.0 m high (shorter duration of 3 to 4 months). Replacement of netting for all zero-grazing units was desirable after the first year of installation, however, farmers could not afford the cost of 100,000 Uganda shillings (approx. USD 30) per zero-grazing unit.