• It is recommended to beat the game normally at least once beforehand. Knowing the map well helps greatly.
  
• Portland is considered to be the best island to do the side-mission on, however it must be done early lest failing to mafia gunfire.
  
• Even if you kept your Ambulance in a garage, start the mission near the accompanying hospital to lose less time in the beginning.
  
• Have the siren turned off. Other cars tend to go all over the place and it is possible for patients to be run over by them.
  
• Unlike in other side-missions, you have to save all patients in one go. The requirement is finishing Level 12.
  
• Drive carefully. The Ambulance is very vulnerable, so every collision counts. Moreover, it is easy to turn over, which is typically hard or impossible to recover from.
  
• Be careful not to run over patients. If a patient is in a location that is hard to reach, be extra careful.
  
• If you accumulate enough time in the timer, take your time to be as careful as possible. If you're running out of time, cut corners as much as possible, but be careful still.
  
• Slow down if approaching a crossing.
  
• Observe the traffic. If a car goes slightly in a direction, it is about to turn to the opposite side.
  
• Avoid chaotic drivers. Their movement is unpredictable.
  
• The Ambulance has space for two in the back and a front passenger seat. Occupy as many slots as possible before driving back — you do not gain time for saving people per se, only for picking them up and finishing a level.
  
• Do not run over any patients after dropping them off or else you may fail the mission.

You can make use of all available passenger space from now on. Remember to use that.

If at this or any earlier point the engine starts emitting smoke, start over.

The final level. Avoid any collisions.

---

Completing Level 12 unlocks Infinite Sprint and counts towards 100% game completion.