The protests were started by students on Monday
Speaking to the Reuters news agency, Mr Meles said he regretted the loss of life but added "things were beginning to get out of control".
"It was prudent to stop this with forceful action," he said.
Mr Meles spoke as rival parties signed a deal backing a call for a probe into claims of fraud in recent elections.
A week of protests against claims of electoral fraud ended in bloodshed on Wednesday.
Mr Meles said he remained ready to take "preventative action" to preserve calm.
Both the ruling Ethiopian People's Revolutionary Democratic Front and the two main opposition coalitions have now backed an inquiry into electoral fraud claims.
Three weeks after polling, final results have not been declared.
Police, meanwhile, arrested some 50 people in the capital, Addis Ababa, as a taxi drivers' strike continued.
Mr Meles insisted that the violence would not derail democracy in Ethiopia, defending the electoral process and its' aftermath: "It's an indication that our democracy is maturing."
After Wednesday's shooting of protesters, European Union observer Ana Gomes condemned the deaths and expressed deep concern at "the dangerous situation Ethiopia was now facing".
The UN Secretary-General, Kofi Annan, and senior ministers from the US and Britain have since called Mr Meles advising restraint, the prime minister said.
Despite blaming one another for the deaths, the ruling EPRDF and the opposition Coalition for Unity and Democracy and United Ethiopian Democratic Forces (UEDF) agreed the deal to let the electoral board investigate more than 300 complaints in the 547 constituencies.
They reaffirmed their commitment to a "peaceful conclusion of the electoral process" and to "make all possible efforts to prevent such violence or incitement to violence [and] to exercise restraint".
"This agreement, if it is... respected by all the parties, will be a signal to calm things down and go back to work, hopefully," National Electoral Board of Ethiopia (NEBE) spokesman Getahun Amognehe told the AFP news agency.
The BBC's Mohammed Adow in Addis Ababa says that Wednesday's shooting began after army special forces arrived at the central business district, where protesters were throwing stones.
However, it is unclear whether the gunfire came from the heavily armed troops or the regular police, our correspondent says.
Wednesday's killings came after two days of student protests in which police beat back protesters with batons and rifle butts, as well as firing warning shots in the air, witnesses said.
The UK Foreign Office has warned citizens travelling in Ethiopia to be cautious and says that tension is spreading to other towns and cities.