The BBC's Animal Hospital, fronted by Rolf Harris, is being taken off air after nearly 10 years.
Harris has presented many heartwarming stories
The weekly stories of animal welfare at an RSPCA hospital have drawn millions of viewers since the show began in 1994.
But producers believe after 19 series it has run its course, and Harris said it was "time to move on".
The show begins its final series on Wednesday, although Harris will return with some one-off specials next year.
Harris, 73, who has just celebrated 50 years in TV, said the weekly show was "very demanding".
He said: "We have had 10 wonderful years with Animal Hospital and although we would like to continue with it forever, we have covered many, many aspects of animal care and welfare with the show and feel that the time has come now to move on."
BBC One controller Lorraine Heggessey said the show had delighted millions of viewers during its run.
"It was the first programme of its kind and spawned many imitations, but it has outlasted them all," she said.
Animal Hospital has shown many heart-rending moments - most famously involving rescue dog Snowy, who was dumped in a police station doorway severely malnourished.
Snowy's plight led to 30,000 viewers offering to adopt her.
It has also featured a number of more exotic pets and complaints, including an iguana with a dislocated toe, a pregnant spider and a dog with a phantom pregnancy.