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Dressel, who also won the men's 100m freestyle gold on Thursday, clocked 21.15 seconds with Brazil's Bruno Fratus taking silver at 0.12 back and Britain's Ben Proud earning bronze at 0.28.
Just half an hour later, Dressel came out and blasted his way to victory in the men's 100m butterfly final. The 20-year-old has now won five golds in Budapest - three individuals titles, including the 100m freestyle, plus victories for the USA in the men's 4x100m freestyle and mixed 4x100m medley.
He could finish with three golds in one night with the 4Ã-100 mixed freestyle relay still to come.
Fratus was pleased with his second silver of the week after finishing second with Brazil in the men's 4x100m freestyle.
"I'm feeling like the silver surfer - I'm feel amusing, it's been the best week of my life, the best to races of my life," said the 28-year-old. "I just feel happy, because I did the hard work, I bust my ass off.
"I don't consider myself a talented guy, but I'm sure a hard worker. "I expected a good time and I got it."
Britain's Proud, who won the 100m butterfly title on Monday, was happy with his second medal of these championships and paid tribute to Dressel, who collected his fourth gold of these world championships.
"It's a really good outcome for me to get third," said the 22-year-old. "I was racing against a guy going 21.1 - you don't see that every day. "It's not often that someone comes along like Caeleb, a really talented swimmer, so third place is better than I expected."
Meanwhile, Sweden's Sarah Sjostrom won the women's 50m butterfly gold at the world championships on Saturday to complete the sprint double. Sjostrom clocked 24.60 seconds, a new championships record, to take gold with Ranomi Kromowidjojo of the Netherlands taking silver at 0.78 back while Egypt's Farida Osman earned bronze at 0.79.
Swedish sprinter Sjostrom completed the butterfly double after winning the women's 100m gold on Monday, also in a record time for the world championships.
It went some way to make up for her disappointment of missing out on gold by just 0.04 in the women's 100m freestyle final on Friday night when she lost to Simone Manuel of the United States on the wall.
"I had a great start, I've been longing for this 50 race all week," said Sjostorm.
"I was really disappointed before this final, I needed just to get it going again. "I've been really strong at the beginning of the races, so I knew it could be good I was looking forward to it." America-born Osman was delighted with her first major medal.
"I'm really happy with that - it was my goal for the whole season," said the 22-year-old University of California student.
"It's a really nice feeling."
Katie Ledecky won her 14th world championship gold medal on Saturday with victory in the women's 800m freestyle final. The 20-year-old clocked eight minutes, 12.68 seconds with China's Li Bingjie taking silver at 2.78 secs back, a new Asian record, and America's Leah Smith claiming bronze at 4.54.
Her victory means Ledecky finishes her championships in Budapest with five golds, from the 400m, 1500m freestyle, 4x100m and 4x200m freestyle, and a 200m freestyle silver.
She has now won 14 titles spanning three world championships.
"It's a great feeling, it's always an honour to represent Team USA at this level of a meet," said Ledecky, the most decorated female swimmer in world championships history. "I always put my best foot forward and do my best."
Ledecky suffered the only defeat of her career in a worlds final when she lost over 200m to Italy's Federica Pellegrini on Wednesday.
"I had some ups and downs this week, but I'm happy to come away with those five golds and a silver," she said. - AFP
"I know I can take a lot away from this week and have learned a lot."
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