The Belgian, who had been out of action since last year's U.S. Open, beat American Abigail Spears 6-4 6-3 to earn a place in the third round of the Nasdaq-100 Open.
"I was pretty nervous but actually it's very normal," Henin-Hardenne told reporters. "Even if everything was not perfect, far from it, I enjoy my tennis and I know I need to be patient.
"Everything will come back with competition and playing a lot of matches. It feels very good, even if it's still hard at the beginning to find the rhythm and everything.
"Just the fact that I'm back on the courts, it's great. That's the only thing that was really important for me today."
The last 12 months have been a frustrating cycle of illness, comeback and injury for the Belgian, dating back to when she was first stricken with the debilitating virus mononucleosis this time last year.
ILL-FATED COMEBACK
Henin-Hardenne made an ill-fated comeback attempt during the clay-court
After going out in the second round at Roland Garros she retreated back to her sickbed and did not return until the Athens Olympics in August.
She won a gold medal in Greece but the effort caught up with her a fortnight later at the U.S. Open and, after reaching the last 16, she did not play again during 2004.
Henin-Hardenne attempted another comeback in January before the Australian Open, only to injure her knee while practising at a warm-up event in Sydney.
"My knee is very good now (but) I lost a lot of confidence last year when there were days I couldn't get up," she said.
"It's been ups and downs. Mentally, it was very, very difficult. Fortunately I got a lot of support from my family, my coach, my friends.
"That helped me a lot with this experience. But it's been really, really hard."
Henin-Hardenne's next opponent in Miami will be Spain's Nuria Llagostera Vives.