Scientist Andrew Booth, 44, made his wife Lorraine, 50, look like a "serious alcoholic" by spiking her drinks, a jury at Sheffield Crown Court was told.
The prosecution allege he eventually killed her by giving her anaesthetic and smothering her with a cushion.
Mr Booth, of Tankersley Lane, Hoyland Common, Barnsley, denies murder.
Divorce settlement
He allegedly stole the anaesthetic from Doncaster Royal Infirmary where he worked as head of biomedical sciences, the court heard.
The couple, who were married for 20 years and had two children, were in the process of a divorce settlement which could have left Mrs Booth with a £60,000 pay-off, the court heard.
The jury was told how Mrs Booth, a barmaid, became concerned when she "passed out" after a couple of glasses of wine at home.
Her stepsister, Katherine Sharp, who lived just yards from the pair, said: "When she was coming home from work, she would have a drink and there were times when she would pass out.
"She told me she felt that Andrew was tampering with the wine in the house."
Ian Strike, who worked with Mrs Booth behind the bar of a local pub, said she was always nervous about going home.
Relatives' concerns
He said one day she had told him she had proof that her husband was "trying to poison her".
Mrs Booth was found dead on the night of 11 July last year at the family home.
A post-mortem examination found no evidence of crime but after relatives took their concerns to the police, a second post-mortem was carried out.
This revealed signs of suffocation and traces of the anaesthetic. It showed no signs of alcoholism.
The court heard how Mr Booth told friends and relatives that his wife had a serious drinking problem and even presented a "drink diary" to her brother and father.
Both men told the court there was nothing to suggest she drank excessively.
The trial continues.
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